Article

Anthropometric characteristics and non-Hodgkin's lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma. In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics. Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14-1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05). The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Components of the MetS have been reported to be associated with an increased risk of cancer incidence and mortality [7,8]. Several cohort studies have shown statistically significant positive associations between body mass index (BMI) and increased risk of lymphoma, in particular, in high-grade B-cell lymphoma [9,10], myeloid leukemia [11], and multiple myeloma [5], whereas others have found no associations between BMI and the overall risk of non-Hodgkin's lymphoma (NHL) [12] or its subtypes [13]. In addition, other metabolic factors such as blood glucose [14] and lipids [15,16] have been linked to an increased risk of blood cancers. ...
... Cox regression models with age as the time variable were fitted to obtain hazard ratios denoted as relative risk with 95 % confidence intervals of blood cancer incidence and mortality in order to control for age, because the cancer incidence is closely related to age. We performed the analyses separately for men and women, because there was evidence for sexdifferential associations [10]. All analyses were performed adjusted for age at baseline (years, continuous), and smoking status (never, current and former smokers, and unknown), since for some entities associations have been observed [20]. ...
... Our findings of a positive association of BMI with lymphoid neoplasms are in line with previous reports [30,31]. Our observation of increased risk of high-grade B-cell NHL among obese individuals is consistent with recent reports from cohort studies [10,30] and pooled analysis [9,24]. Experimental studies have shown that leptin induced the proliferation and differentiation of hematopoietic cells [32] and modulates the immune function in the hematopoietic process, particularly in the B-cell compartment [33]. ...
Article
Full-text available
We investigated associations between metabolic factors and blood cancer subtypes. Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol, and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean age = 44 years). Relative risks of blood cancers were calculated from Cox regression models. During mean follow-up of 12 years, 2,751 incident and 1,070 fatal cases of blood cancers occurred. Overall, higher BMI was associated with an increased blood cancer risk. In gender-specific subgroup analyses, BMI was positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p = 0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were inversely associated with myeloid neoplasms in women (p = 0.01), particularly acute myeloid leukemia (p = 0.003), and glucose was positively associated with chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively associated with risk of high-grade B-cell lymphoma and multiple myeloma, while cholesterol was inversely associated with low-grade B-cell lymphoma. The metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma among women. BMI showed up as the most consistent risk factor, particularly in women. A clear pattern was not found for other metabolic factors.
... (i.e., at cohort entry); only a few studies assessed BMI at different ages throughout adult life (4)(5)(6)(7) or evaluated additional measures of adiposity, such as waist circumference or waist-to-hip ratio (WHR) (5,(8)(9)(10). Furthermore, to our knowledge, only one study evaluated multiple myeloma incidence in relation to physical activity (11). ...
... Findings from previous studies of multiple myeloma risk in relation to waist circumference have been inconsistent. Waist circumference was positively associated with multiple myeloma risk in the Iowa Women's Health Study (8), but other studies found no association among women (5) or in sexspecific (9) or sex-combined (10) analyses. Findings from prior studies of multiple myeloma risk in relation to WHR have been null (5,(8)(9)(10), similar to what we found. ...
... Waist circumference was positively associated with multiple myeloma risk in the Iowa Women's Health Study (8), but other studies found no association among women (5) or in sexspecific (9) or sex-combined (10) analyses. Findings from prior studies of multiple myeloma risk in relation to WHR have been null (5,(8)(9)(10), similar to what we found. Collectively, results from the present study and other studies suggest that overall adiposity, rather than abdominal adiposity, may be a risk factor for multiple myeloma. ...
Article
Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995-1996; n = 485,049), and a subset of participants completed a second questionnaire (1996-1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m(2) increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk.
... 11 Risk factors for MGUS were studied using available survey information (including medical exams, routine blood tests, questionnaires concerning medical history, nutrition, and demographics) available from NHANES. We first conducted risk factor analyses involving a pre-defined set of variables that, based on prior studies, have been suggested as having potential associations with MGUS, namely body mass index (BMI), [16][17][18] socioeconomic status (SES), 16,19 immunostimulatory factors, [17][18][19][20][21] smoking, vitamin D, 20,21 and pesticide exposure. 22,23 We explored the role of SES by using educational and poverty index ratio as proxy markers. ...
... 11 Risk factors for MGUS were studied using available survey information (including medical exams, routine blood tests, questionnaires concerning medical history, nutrition, and demographics) available from NHANES. We first conducted risk factor analyses involving a pre-defined set of variables that, based on prior studies, have been suggested as having potential associations with MGUS, namely body mass index (BMI), [16][17][18] socioeconomic status (SES), 16,19 immunostimulatory factors, [17][18][19][20][21] smoking, vitamin D, 20,21 and pesticide exposure. 22,23 We explored the role of SES by using educational and poverty index ratio as proxy markers. ...
... On further analysis, there was a trend to higher risk of MGUS with increasing BMI (Table 3). Smaller studies [16][17][18]27 have associated obesity with an excess risk of MGUS and MM, and the present study provides supporting evidence for this association. [16][17][18]27 However, our attempt to explain this association by assessing mechanistic associations with factors such as C-peptide, insulin, or glucose levels did not reveal additional correlations. ...
Article
Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the United States (U.S.) population. Stored serum samples from National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999-2004 were available for 12 482 persons age 50 years (2331 'black', 2475 Hispanics, 7051 'white', and 625 'others') on which agarose-gel electrophoresis, serum protein immunofixation, serum free light-chain assay, and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the U.S., respectively (P=0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in prevalence of MGUS between the North/Midwest versus the South/West regions of the U.S. was found, which has etiologic implications.Leukemia accepted article preview online, 20 January 2014. doi:10.1038/leu.2014.34.
... We evaluated the association of 20-year weight patterns in adulthood, trajectory of body shape through age 60 years, and measures of central and peripheral adiposity with MM risk using data from two large cohorts. Our objective was to confirm and expand on previous investigations of these exposures (11,(13)(14)(15)(16)(17)(18) with a larger number of cases and longer duration of follow-up (than most)-as well as with a novel life course approach-to optimize strategies regarding obesity and MM prevention. ...
... A study of MM mortality in 1.5 million participants pooled from 20 cohorts (n ¼ 1388 MM deaths) found a positive association for waist circumference and a suggestive positive association for WHR (13). However, two earlier cohort studies with limited case numbers observed no statistically significant association for waist circumference or WHR with lymphoproliferative cancers (combined) or MM (16,18). The current analysis found no statistically significant associations between central adiposity, as assessed by waist circumference and WHR, and MM risk. ...
... Our observation that a larger hip circumference was associated with increased MM risk is consistent with an earlier prospective study of 37 083 postmenopausal women (n ¼ 95 MM cases) that reported a statistically significant trend for increased MM risk across tertiles of hip circumference (15). Although this association is intriguing, the mechanistic interpretation is unclear, and several other investigations observed no association of hip circumference with MM risk (14,16,18). Limitations include the fact that our primary exposure variables are based on self-reported data and, although prospectively assessed and validated (22,25), are subject to misclassification. ...
Article
Full-text available
Background: Although obesity is an established modifiable risk factor for multiple myeloma (MM), several nuanced aspects of its relation to MM remain unelucidated, limiting public health and prevention messages. Methods: We analyzed prospective data from the Nurses' Health Study and Health Professionals Follow-Up Study to examine MM risk associated with 20-year weight patterns in adulthood, body shape trajectory from ages 5 to 60 years, and body fat distribution. For each aforementioned risk factor, we report hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MM from multivariable Cox proportional-hazards models. Results: We documented 582 incident MM cases during 4 280 712 person-years of follow-up. Persons who exhibited extreme weight cycling, for example, those with net weight gain and one or more episodes of intentional loss of at least 20 pounds or whose cumulative intentional weight loss exceeded net weight loss with at least one episode of intentional loss of 20 pounds or more had an increased MM risk compared with individuals who maintained their weight (HR = 1.71, 95% CI = 1.05 to 2.80); the association was statistically nonsignificant after adjustment for body mass index. We identified four body shape trajectories: lean-stable, lean-increase, medium-stable, and medium-increase. MM risk was higher in the medium-increase group than in the lean-stable group (HR = 1.62, 95% CI = 1.22 to 2.14). Additionally, MM risk increased with increasing hip circumference (HR per 1-inch increase: 1.03, 95% CI = 1.01 to 1.06) but was not associated with other body fat distribution measures. Conclusions: Maintaining a lean and stable weight throughout life may provide the strongest benefit in terms of MM prevention.
... I 2 ¼45%, P heterogeneity ¼0.02) for NHL (20 studies [10-12, 23, 24, 27-31, 33, 34, 36, 39-42, 58]; Figure 3), 1.11, 95%CI ¼ 1.05-1.16, I 2 ¼16%, P heterogeneity ¼0.29) for DLBCL (18 studies [11,12,24,26,29,30,32,33,36,42,48]; supplementary Figure S1, available at Annals of Oncology online), and 1.03 (95%CI ¼ 0.98-1.09, I 2 ¼3%, P heterogeneity ¼0.41) for FL (19 studies [11, 12, 24, 26, 29, 30, 32, 33, 36, 42, 48]; supplementary Figure S2, available at Annals of Oncology online). ...
... The summary RR per 5 cm increment of height was 1.05 (95%CI ¼ 1.02-1.08, I 2 ¼1%, P heterogeneity ¼0.42, 8 studies [12,15,25,30,32,43,63,64]) ( Table 1; supplementary Figure S28, available at Annals of Oncology online). There was no evidence of publication bias (P-value for Egger's test¼0.64). ...
... I 2 ¼70%, P heterogeneity ¼ 0.01) for NHL (5 studies [24,28,29,33,42]) (supplementary Figure S32, available at Annals of Oncology online), 1.03 (95%CI ¼ 0.98-1.07, I 2 ¼22%, P heterogeneity ¼0.89) for DLBCL (6 studies [24,29,32,33,42,48]) (supplementary Figure S33, Figure 4. Dose-response meta-analysis of BMI and risk of multiple myeloma cancer risk. RR, relative risk; 95% CI, 95% confidence interval. ...
Article
Full-text available
Background: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. Method: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). Results: Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. Conclusion: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.
... The European Prospective Investigation into Cancer and Nutrition highlighted a possibly higher risk of lymphoma MM in taller women. 20 The prospective American Cancer Society Cancer Prevention Study-II Nutrition Cohort also supported an association between height and risk of non-Hodgkin lymphoma (NHL), most strongly with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and to a lesser extent with MM. 21 To our knowledge, no meta-analysis has been undertaken to examine the associations between adult attained height and risk of hematological malignancies. ...
... 21 were excluded due to overlap with the pooled analysis by Teras et al. 44 Furthermore, five eligible articles were yielded from the "snowball" procedure 48,50-53 and, finally, a total of 44 studies were deemed eligible for inclusion. 20,21,41, The characteristics of eligible studies are shown in Supporting Information Table S1. The successive steps during the selection of studies are depicted in Supporting Information Figure S1. ...
... The ascertainment of exposure often suffered from selfreporting, a fact which signals the existence of reporting bias. Nearly half of studies met the criterion of representativeness, 20 as many studies were based on cohorts selected in terms of age, profession or other factors. Although adjustment was performed in all studies, the factors that were included in multivariate models were not uniform across the included studies. ...
Article
Overweight/obesity, adult attained height and physical activity are possible risk factors for hematological malignancies. This meta‐analysis aims to evaluate the associations between these factors and hematological cancer risk in adults. Eligible cohort studies were sought in PubMed up to May 31, 2016; overall, 44 studies were included in the present analyses. Pooled relative risk (RR) estimates were calculated using random‐effects models; separate analyses were conducted for non‐Hodgkin lymphoma (NHL) and subtypes (diffuse large B‐cell lymphoma, DLBCL; follicular cell lymphoma, FCL; small lymphocytic lymphoma/chronic lymphocytic leukemia, SLL/CLL), Hodgkin lymphoma (HL), multiple myeloma (MM), leukemia and subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, AML). Obesity was associated with increased risk of NHL, HL, MM, leukemia overall and AML in both sexes, as well as with higher DLBCL risk in women; the dose‐response meta‐regression analysis confirmed these associations. Less pronounced effects were observed regarding overweight, as it was associated with increased MM risk in both sexes, NHL risk in males, DLBCL and overall leukemia risk in females. Taller men presented with significantly higher risk of NHL and taller women were affected by higher risk of NHL, DLBCL, FL, CLL/SLL, MM, leukemia and AML. On the other hand, physical activity and abdominal fatness were not associated with the risk of hematological malignancies. In conclusion, this meta‐analysis highlights the pivotal role of anthropometric measures in shaping the risk of hematological malignancies in adults. Additional, well‐designed studies stemming from all the continents are needed for the further substantiation and generalization of the results. This article is protected by copyright. All rights reserved.
... The other two recent prospective studies also found significant positive associations between obesity and NHL risk (20,22). However, out of a current total of 22 prospective cohort studies, only 3 studies took into account the presence or absence of diabetes in the analyses (24)(25)(26). These studies adjusted their analyses for diabetic status (24)(25)(26), raising the possibility that many of the reported associations, while statistically significant, may be attenuated due to the inclusion of type 2 diabetics and pre-diabetics (see Section "Design Considerations for Studies of Obesity-Related Hormones and Adipocytokines in the Etiology Studies of Cancer" regarding study design considerations). ...
... However, out of a current total of 22 prospective cohort studies, only 3 studies took into account the presence or absence of diabetes in the analyses (24)(25)(26). These studies adjusted their analyses for diabetic status (24)(25)(26), raising the possibility that many of the reported associations, while statistically significant, may be attenuated due to the inclusion of type 2 diabetics and pre-diabetics (see Section "Design Considerations for Studies of Obesity-Related Hormones and Adipocytokines in the Etiology Studies of Cancer" regarding study design considerations). Only 2 of the 22 studies accounted for the use of HT or menopause status (25,27), raising similar considerations of possibly attenuated associations. ...
Article
Full-text available
This article presents the first detailed overview of the mechanisms that may underlie the relation of obesity with B-cell non-Hodgkin lymphomas (NHLs) and multiple myeloma (MM). Epidemiologic studies, including meta-analyses of prospective cohorts, have reported that the risks of NHL and MM are significantly increased in obese, relative to normal weight, women and men. Accumulating experimental and clinical evidence suggests that inflammatory cytokines, hyperinsulinemia, and sex hormones could play a role in the association of obesity with B-cell NHL and MM carcinogenesis. There is, however, a paucity of data published from appropriate large prospective cohort studies, and studies concurrently measuring these correlated factors, to formally determine the likely biologic factors driving the relationship of obesity with NHL and MM. Additional strengths and weaknesses of the current literature, as well as study design issues that need to be considered in conducting these studies, such as the exclusion of type 2 diabetics or postmenopausal women using hormone therapy, are discussed.
... These null associations with anthropometric measures are consistent with findings from a nationwide Swedish cohort study and the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study (15,16), but not U.S. cohort studies among men and women (Nurses' Health Study and Cancer Prevention Study cohorts) (17,18). However, recent meta-analyses comprising a combined 8,982 incident multiple myeloma cases reported a modest 20% increase in MM risk among obese persons in both cohort (6) and case-control studies (5,19). ...
... Differences in MM tumor characteristics by sex have previously been reported; female patients have more IgH translocations and inferior survival, whereas male patients have more frequent hyperdiploidy (28). Some epidemiologic associations have also varied by sex; for example, in the European Prospective Investigation on Cancer study, height was associated with increased MM risk among women but not men, and higher weight was associated with increased MM risk among men only (16). These differences could be due to chance, but biochemical studies have reported lower estrogen levels and a decreased estrogen-to-testosterone ratio among women with MM than women without MM (29, 30). ...
Article
Background: Risk of developing multiple myeloma (MM) rises with age and is greater among men and blacks than among women and whites, respectively, and possibly increased among obese persons. Other risk factors remain poorly understood. By pooling data from two complementary epidemiologic studies, we assessed whether obesity, smoking, or alcohol consumption alters MM risk and whether female reproductive history might explain the lower occurrence of MM in females than in males. Methods: The Los Angeles County MM Case-Control Study (1985-1992) included 278 incident cases and 278 controls, matched on age, sex, race, and neighborhood of residence at case's diagnosis. We estimated MM risk using conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). In the prospective California Teachers Study (CTS), 152 women were diagnosed with incident MM between 1995 and 2009; we calculated hazard ratios using Cox proportional hazards analysis. Data from the two studies were pooled using a stratified, nested case-control sampling scheme (10:1 match) for the CTS; conditional logistic regression among 430 cases and 1,798 matched controls was conducted. Results: Obesity and smoking were not associated with MM risk in the individual or combined studies. Alcohol consumption was associated with decreased MM risk among whites only (pooled OR = 0.66, 95% CI = 0.49-0.90) for ever versus never drinking. Higher gravidity and parity were associated with increased MM risk, with pooled ORs of 1.38 (95 % CI = 1.01-1.90) for ≥3 versus 1-2 pregnancies and 1.50 (95% CI = 1.09-2.06) for ≥3 versus 1-2 live births. Conclusions: Female reproductive history may modestly alter MM risk, but appears unlikely to explain the sex disparity in incidence. Further investigation in consortial efforts is warranted.
... Our initial search rendered 1778 returns, from which a total of 16 prospective cohort studies on incidence [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and 6 on mortality [21,[29][30][31][32][33] were included (Fig. 1). The characteristics of the studies included in this meta-analysis are shown in Table 1. ...
... Ten studies reported on the incidence of CLL [13][14][15]17,20,[22][23][24][25]27]. The RR of CLL was increased in obese and overweight individuals (p < 0.001 and p = 0.002, respectively). ...
Article
The main objectives of the present meta-analysis of prospective cohort studies were to evaluate the role of obesity on the incidence and mortality of leukemia in adults. Obesity was associated with a relative risk (RR) of 1.26 (95% CI 1.17-1.37; p < 0.001) for leukemia incidence and 1.29 (95% CI 1.11-1.49; p = 0.001) for mortality. Obesity was also associated with an increased incidence of acute myeloid leukemia (RR 1.53, 95% CI 1.26-1.85; p<0.001), chronic lymphocytic leukemia (RR 1.17, 95% CI 1.08-1.27; p < 0.001), chronic myeloid leukemia (RR 1.16, 95% CI 1.04-1.30; p = 0.007) and acute lymphoblastic leukemia (RR 1.62, 95% CI 1.12-2.32; p = 0.009). The risk of incidence and mortality of leukemia in adults was consistently higher in obese men.
... In our study, waist circumference, but not waist-to-hip ratio, was an independent risk factor for multiple myeloma mortality. In contrast to our findings, two smaller multiple myeloma incidence studies (Britton et al, 2008;MacInnis et al, 2005) reported no association with waist circumference. However, both the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 268 multiple myelomas; Britton et al, 2008) and the Melbourne Collaborative Cohort (n = 55 multiple myelomas, MacInnis et al, 2005) observed no association with BMI. ...
... In contrast to our findings, two smaller multiple myeloma incidence studies (Britton et al, 2008;MacInnis et al, 2005) reported no association with waist circumference. However, both the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 268 multiple myelomas; Britton et al, 2008) and the Melbourne Collaborative Cohort (n = 55 multiple myelomas, MacInnis et al, 2005) observed no association with BMI. Again, limited power may explain these results. ...
Article
Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1·5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR = 1·22, 95% CI: 1·09-1·35 per 5 kg/m(2) ) and for higher cohort-entry BMI (HR 1·09, 95% CI: 1·03-1·16 per 5 kg/m(2) ) and waist circumference (HR = 1·06, 95% CI: 1·02-1·10 per 5 cm). Women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18·5 ≤ 25 at both time points (HR = 1·95, 95% CI: 1·33-2·86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood.
... The association of overweight and obesity in early adulthood with FL risk is strengthened by the significant positive doseresponse trend of early adult BMI with FL risk. However, most cohort studies (7,56,58,(77)(78)(79)(80)(81)(82), with one exception (83), found no relationship of early adult weight or BMI with FL, although many of these studies included relatively small numbers of FL cases. Our finding of a relationship between greater adult height in males, but not females, in relation to FL is likely a chance finding since most cohort studies (56,58,(78)(79)(80)(81)(82) reported no relationship of height in men or women with FL except for three (20,77,83) that found a positive relationship in women. ...
... However, most cohort studies (7,56,58,(77)(78)(79)(80)(81)(82), with one exception (83), found no relationship of early adult weight or BMI with FL, although many of these studies included relatively small numbers of FL cases. Our finding of a relationship between greater adult height in males, but not females, in relation to FL is likely a chance finding since most cohort studies (56,58,(78)(79)(80)(81)(82) reported no relationship of height in men or women with FL except for three (20,77,83) that found a positive relationship in women. This pooled analysis is the first and largest multivariate assessment of a broad range of putative risk factors for FL. ...
Article
Full-text available
Background: Follicular lymphoma (FL) has been linked with cigarette smoking and, inconsistently, with other risk factors. Methods: We assessed associations of medical, hormonal, family history, lifestyle, and occupational factors with FL risk in 3530 cases and 22639 controls from 19 case-control studies in the InterLymph consortium. Age-, race/ethnicity-, sex- and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Results: Most risk factors that were evaluated showed no association, except for a few modest or sex-specific relationships. FL risk was increased in persons: with a first-degree relative with non-Hodgkin lymphoma (OR = 1.99; 95% CI = 1.55 to 2.54); with greater body mass index as a young adult (OR = 1.15; 95% CI = 1.04 to 1.27 per 5 kg/m(2) increase); who worked as spray painters (OR = 2.66; 95% CI = 1.36 to 5.24); and among women with Sjögren syndrome (OR = 3.37; 95% CI = 1.23 to 9.19). Lower FL risks were observed in persons: with asthma, hay fever, and food allergy (ORs = 0.79-0.85); blood transfusions (OR = 0.78; 95% CI = 0.68 to 0.89); high recreational sun exposure (OR = 0.74; 95% CI = 0.65 to 0.86, fourth vs first quartile); who worked as bakers or millers (OR = 0.51; 95% CI = 0.28 to 0.93) or university/higher education teachers (OR = 0.58; 95% CI = 0.41 to 0.83). Elevated risks specific to women included current and longer duration of cigarette use, whereas reduced risks included current alcohol use, hay fever, and food allergies. Other factors, including other autoimmune diseases, eczema, hepatitis C virus seropositivity, hormonal drugs, hair dye use, sun exposure, and farming, were not associated with FL risk. Conclusions: The few relationships observed provide clues suggesting a multifactorial etiology of FL but are limited in the extent to which they explain FL occurrence.
... Previous studies have reported height as a risk factor for NHL. 3,6,21,22,[25][26][27][28] However, in an analysis that combined 18 studies from 13 countries, the tallest men were found to have a minimally greater risk in comparison with men of midrange height. 9 Among the NHL histological subtypes in our study, the most prominently elevated risk for the tallest group was associated with DLBCL and PCL. ...
... In addition to genetics, height can be affected by nutrition and exposure to childhood and adolescent diseases. 25 Lu et al 21 described possible pathways underlying the link between height and the risk of NHL. Height and excess nutrition in childhood have been related to higher IGF-1 levels, 31,[41][42][43][44] which have an important effect on growth hormone and childhood growth. ...
Article
Background: The age-adjusted annual incidence of non-Hodgkin lymphoma (NHL) has risen worldwide. This trend may be affected by the secular increase in height and the sharp upswing in adolescent overweight; these drive increased insulinlike growth factor 1 and chronic inflammation, which may play an etiologic role. This study examined the association of the body mass index (BMI) and height of adolescents with NHL subtypes, which have been insufficiently evaluated. Methods: Health-related data on 2,352,988 Israeli adolescents, aged 16 to 19 years, who were examined between 1967 and 2011 were linked to the Israel National Cancer Registry to derive the NHL incidence up to December 31, 2012 (4021 cases). Cox proportional hazards modeling was used to estimate the multivariate-adjusted hazard ratio (HR) for NHL subtypes associated with the BMI and height of adolescents. Results: Adolescent overweight and obesity were associated with an HR of 1.25 (95% confidence interval [CI], 1.13-1.37; P = 1.14 × 10(-5) ) for NHL in comparison with normal weight. There was a graded association of height with NHL (P = 4.29 × 10(-9) ), with the tallest adolescents (≥95th percentile vs 25th to < 50th percentiles [US Centers for Disease Control and Prevention]) exhibiting an HR of 1.28 (95% CI, 1.04-1.56). Marginal zone lymphoma, primary cutaneous lymphoma (PCL), and diffuse large B-cell lymphoma (DLBCL) showed the strongest associations for overweight/obesity, and DLBCL and PCL showed the strongest associations for height. Conclusions: The findings of this large cohort study add to the growing body of evidence showing that higher body weight and taller stature during adolescence are associated with an increased risk of NHL and may modestly contribute to its increasing incidence. Further studies are needed to elucidate the mechanisms linking anthropometric measures and NHL risk. Cancer 2015;000:000-000. © 2015 American Cancer Society.
... One study showed that pathological WC was associated with increased risk for myeloid leukemia, whereas no association was observed with lymphoid malignancies [26]. The lack of association between waist measurements and risk of NHL has been confirmed in other studies [27,28]. In contrast, data from the literature indicate an association between WC and risk of MM [29,30]. ...
Article
Full-text available
High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmö Diet and Cancer study conducted in Sweden between 1991–1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.
... However, in the present study, we could not obtain this detailed clinical information. We did find a new association between WC and lymphoma/ brain tumours, which has not been previously reported because the BMI was not adjusted in previous studies 47,48 . In contrast, we could not find an association for leukaemia that has previously been reported to be associated with central adiposity 49 . ...
Article
Background: Large waist circumference (WC) is a risk factor for several site-specific cancers, but a large-scale systematic investigation across all common cancers adjusted for potential confounders has not been conducted. This study aimed to evaluate the possible links between WC and common cancers. Methods: We prospectively examined the association between WC and the risk of cancers in a 7-year cohort study of nearly 22.9 million Korean adults. Using the claims database merged with the national health check-up data, we fitted proportional hazard models to investigate associations between WC and 23 of the most common cancers, with adjustment for potential confounders, including body mass index (BMI). We also evaluated the modification of BMI on the relationships between WC and the incidence of cancer. Results: A total of 769,871 cancer cases were identified. WC was positively associated with 18 of 23 cancers, and the effects varied substantially by site in each sex. The modification of BMI on the WC-cancer association also varied across the cancer site; in most cases it mitigated the association. For cancers of the oral cavity, larynx, oesophagus, lung, and premenopausal breast, the BMI adjustment reversed the association toward being positive (all Ptrend < 0.001). Conclusions: Central obesity, independent of general obesity, was associated with the risk of several cancers. The heterogeneity in the mediating effects of BMI suggests that different mechanisms are associated with different cancer sites. Based upon these findings, active strategies to monitor and prevent central obesity should be implemented.
... All studies of smoking and alcohol history relied on self-administered questionnaires except for one cohort study [39], where a structured interview was conducted. Information on weight and height was self-reported in most studies, while in three cohort studies [42,44,45] and one case-control study [58], weight and height were measured by a trained interviewer or technician. All studies except two [41,43] used the World Health Organization (WHO) standard for categorizing BMI. ...
Article
Full-text available
PurposeTo investigate the relationship between follicular lymphoma (FL) risk and common modifiable lifestyle factors, specifically smoking, alcohol, body mass index (BMI), and hair dye use.Methods We performed a systematic review and meta-analysis of observational studies published prior to 01 January 2020. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science and the reference lists of original studies and review articles. We used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95% CI).ResultsTwenty-four cohort and ten case–control studies were eligible. Ten articles examined smoking, 11 alcohol, 13 BMI, and four hair dye use and risk of FL. The meta-estimate for current smoking was 1.11 (95% CI 0.92–1.35; I2 = 51%) and there was no significant dose–response per 5-year increase in duration (p-trend = 0.087). Current alcohol intake was inversely associated with FL risk (meta-RR 0.87, 95% CI 0.81–0.94; I2 = 0%) and there was a significant dose–response per 5 drinks/week increase in intake (p-trend = 0.008). There was no association with 5 kg/m2 increase in early adulthood BMI (meta-RR 1.05, 95% CI 0.91–1.20; I2 = 7%) or being overweight (meta-RR 0.99, 95% CI 0.92–1.07; I2 = 0%) or obese (meta-RR 1.08, 95% CI 0.99–1.17; I2 = 0%) as an adult. Hair dye use before 1980 was positively associated with FL risk (meta-RR 1.66, 95% CI 1.22–2.25; I2 = 55%) and no evidence of effect after 1980.Conclusion We found consistent evidence of an inverse association between current alcohol intake and FL risk, and a significant increased risk with hair dye use before 1980. The evidence for smoking is heterogeneous, but most studies did not support an association. Further research is required to understand the mechanisms underlying these associations and the potential for prevention strategies.
... WC was positively associated with ovarian, 45 46 Hodgkin's lymphoma and multiple myeloma. 47 WHtR was strongly associated with hepatocellular carcinoma. 46 The identification of visceral obesity risk in several types of cancer is important in order to determine the specific targets of preventive public health programs. ...
Article
Full-text available
Evidence shows a strong relationship between obesity, cancer and cardiovascular disease (CVD) risk. However, there is not enough evidence of the role of visceral obesity on both CVD and cancer. Visceral obesity may be more pro-oncogenic than total body fat. Therefore, it is important to know whether abdominal obesity can lead to both CVD and cancer. The present integrative review aimed at evaluating epidemiological evidence on the potential connection of visceral obesity in the occurrence of cancer and CVD. The following databases were searched: SCOPUS, PubMed, Science Direct, Lilacs, SciELO, Google Scholar, Web of Science, Scopus and ProQuest. The presence of visceral obesity can increase the risk of some specific cancer types, but there is controversial evidence about CVD risk based on sex-specific and ageing analyses. There is enough evidence that visceral obesity increases the risk of colorectal, pancreatic and gastro-oesophageal cancer. However, for some types of cancer such as breast, endometrial and renal, visceral obesity is a risk only in post-menopausal women. Regarding prostate cancer, the evidence is controversial. Despite the risk of visceral obesity being consistently associated with CVD in adults, this association disappears in sex-specific and older adults analyses. Moreover, in older adults, the results are controversial due to the use of different measures such as waist circumference and visceral adipose tissue. However, the evidence showing visceral obesity as a risk factor to CVD remains controversial. Sex differences, ageing and body mass index (BMI) category can potentially modify this association. Therefore, further epidemiological studies with analyses stratified by sex and samples including older adults aged 65 and older are needed. K E Y W O R D S aging, body composition, visceral adiposity, waist circumference
... In epidemiologic studies, taller adult height has been associated with an increased risk of several subtypes of non-Hodgkin lymphoma (NHL) (1); however, the results have not been consistent across studies for common subtypes, such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small cell lymphoma (CLL) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Taller height has also been positively associated with other cancers in both epidemiologic and Mendelian randomization studies (14)(15)(16). ...
Article
Full-text available
Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
... Using ICD-O-3, we found increased risks of both lymphoid and myeloid cancer, and of many subtypes. Positive associations have been previously reported for lymphoproliferative and myeloproliferative malignancies both separately and combined (Engeland et al, 2007), and for Hodgkin lymphoma (Engeland et al, 2007), diffuse large B-cell lymphoma (Troy et al, 2010), follicular lymphoma (Cerhan et al, 2005; Britton et al, 2008), plasma cell neoplasms (Engeland et al, 2007), CLL/SLL (Lu et al, 2009; Troy et al, 2010), and acute myeloid leukaemia (Engeland et al, 2007). One study analysed mature T-cell disease but found no significant association (Lim et al, 2007). ...
Article
Full-text available
Background: Greater adiposity and height have been associated with increased risk of haematological malignancies. Associations for disease subtypes are uncertain. Methods: A cohort of 1.3 million middle-aged UK women was recruited in 1996–2001 and followed for 10 years on average. Potential risk factors were assessed by questionnaire. Death, emigration, and incident cancer were ascertained by linkage to national registers. Adjusted relative risks were estimated by Cox regression. Results: During follow-up, 9162 participants were diagnosed with lymphatic or haematopoietic cancers. Each 10 kg m−2 increase in body mass index was associated with relative risk of 1.20 (95% confidence interval: 1.13–1.28) for lymphoid and 1.37 (1.22–1.53) for myeloid malignancy (P=0.06 for heterogeneity); similarly, Hodgkin lymphoma 1.64 (1.21–2.21), diffuse large B-cell lymphoma 1.36 (1.17–1.58), plasma cell neoplasms 1.21 (1.06–1.39), acute myeloid leukaemia 1.47 (1.19–1.81), and myeloproliferative/myelodysplastic syndromes 1.32 (1.15–1.52). Each 10 cm increase in height was associated with relative risk of 1.21 (1.16–1.27) for lymphoid and 1.11 (1.02–1.21) for myeloid malignancy (P=0.07 for heterogeneity); similarly, mature T-cell malignancies 1.36 (1.03–1.79), diffuse large B-cell lymphoma 1.28 (1.14–1.43), follicular lymphoma 1.28 (1.13–1.44), plasma cell neoplasms 1.12 (1.01–1.24), chronic lymphocytic leukaemia/small lymphocytic lymphoma 1.23 (1.08–1.40), and acute myeloid leukaemia 1.22 (1.04–1.42). There was no significant heterogeneity between subtypes. Conclusion: In middle-aged women, greater body mass index and height were associated with modestly increased risks of many subtypes of haematological malignancy.
... Although not all previous studies (9-11) have reported positive associations between BMI in adulthood and risk of NHL, the bulk of the more recent epidemiologic literature supports a weak positive association between obesity and NHL overall, with the most consistent evidence apparent for the DLBCL subtype (5,8). Several prior studies have evaluated central adiposity as measured by waist circumference and waist-to-hip ratio (9,11,(25)(26)(27); most have found no association. ...
Article
The etiology of non-Hodgkin lymphoma (NHL) is poorly understood. Obesity is associated with inflammation, a cytokine milieu conducive to lymphocyte proliferation, and has been associated with NHL risk in some epidemiologic studies. To prospectively examine NHL risk in relation to adult and earlier life obesity, we documented 635 incident NHL diagnoses among 46,390 men in the Health Professionals Follow-up Study and 1254 diagnoses among 116,794 women in the Nurses' Health Study over 22-32 years of follow-up. Using multivariable Cox proportional hazards models we estimated cohort-specific incidence rate ratios (RRs) and 95% confidence intervals (CI) for risk of NHL and major histologic subtypes associated with cumulative average middle and young adult (ages 18-21) body mass index (BMI) and adolescent and childhood somatotype. NHL risk was modestly increased in men (but not women) with a cumulative average middle adult BMI ≥30 kg/m2 (vs. 15-22.9 kg/m2; RR: 1.28; 95% CI: 0.92, 1.77; P-trend=0.05). In meta-analyses across cohorts, higher young adult BMI was associated with increased risk of all NHL (pooled RR per 5 kg/m2: 1.19; 95% CI: 1.05, 1.37), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (all P-trend≤0.02). Adolescent somatotype was also positively associated with all NHL, DLBCL, and FL in pooled analyses (all P-trend ≤0.03) while childhood somatotype was positively associated with NHL overall among women only (P-trend <0.01). These findings in two large prospective cohorts provide novel evidence that larger body size in childhood, adolescence, and young adulthood predicts increased risk of NHL, and particularly of DLBCL and FL.
... Our PubMed search rendered 560 articles, from which we included 16 epidemiologic studies, 6 case-control studies, 8,[18][19][20][21][22] and 10 prospective cohort studies. 5,6,[23][24][25][26][27][28][29][30] The search flow is shown in Figure 1. Our search on EMBASE and the Cochrane Database Table 3. Forest plots are shown in Figure 2. ...
Article
Introduction The relation between body mass index (BMI) and incidence of diffuse large B-cell lymphoma (DLBCL) has been suggested but no systematic review has been undertaken. Methods We performed a literature search through December 2012. Meta-analyses were performed to quantify the relative risk (RR) of DLBCL incidence in overweight and obese compared with normal weight individuals using the random-effects model. Subset analyses were performed according to study design, sex and geographical region. Overweight was defined as BMI 25–29.9 kg/m2 and obesity as BMI 30 kg/m2. Meta-regression using an unrestricted maximum likelihood model was performed to evaluate the linear association between BMI and odds of DLBCL. Results Our study included six case-control and ten cohort studies. The RR of DLBCL in overweight individuals was RR 1.14 (95% CI 1.04-1.24; p=0.004), and in obese 1.29 (95% CI 1.16-1.43; p<0.001). The RR of DLBCL in overweight men and women were 1.22 and 1.27, respectively. In overweight individuals, both prospective and case-control studies showed a RR of 1.13. The RR of DLBCL in obese men and women were 1.40 and 1.34, respectively. In obese individuals, the RR in prospective studies was 1.25 and in case-control 1.33. Meta-regression analysis showed a 14% increase in DLBCL incidence for each 10 kg/m2 increase in BMI. Conclusion An increased BMI is associated with higher RR of DLBCL regardless of sex. Also, there seems to be a linear association between BMI and DLBCL incidence.
... For example, a potential explanation for the lower rates in the southern areas might be the relatively lower height of their residents. Previous studies reported a modest increased risk for taller individuals (20)(21)(22)(23). Further investigation is needed to investigate and find the causes. ...
Article
Full-text available
Multiple myeloma (MM) is the second most frequent malignancy of blood, and information on disease burden of MM is limited in developing countries. We aimed to estimate the prevalence and incidence of MM in China. We used data from the national urban employee and urban resident basic medical insurance from 2012 to 2016 in China. MM cases were based on the primary diagnosis (International Classification of Diseases (ICD) code, ICD for oncology, or text of diagnosis) of patients. The crude prevalence and incidence were 6.88 per 100,000 population (95% CI, 5.75–8.00) and 1.60 per 100,000 person-years (1.28–1.92), respectively. The standardized prevalence and incidence were 5.68 (5.64–5.72) and 1.15 (1.11–1.19), respectively. Overall, the rates were higher in males compared with females for prevalence (7.89 vs. 5.79, P < 0.05) and incidence (1.84 vs. 1.30, P < 0.05). Both rates increased with age, and the mean age (SD) of MM patients was 57.9 (14.4) years. Prevalence peaked between 55 and 74 years old for both genders. The incidence in women aged 55–59 had a significantly high incidence of 5.53 (4.98–6.11). The prevalence and incidence were significantly lower than those in North America, Australia, and Western Europe but were in the same range as those in Japan or Korea. MM should be one of the cancers in the spotlight from both medical and socioeconomic perspectives in low-resource but populous countries because of the incidence of more elderly MM patients in the next decade. Further research is warranted to examine the potential pathophysiologic mechanism.
... Obesity is associated with a 1.5-to 2-fold elevated risk of developing MM, suggesting that it has a role in myelomagenesis. [1][2][3] Several cytokines and growth factors that promote MM growth, such as tumor necrosis factor a, interleukin 6, MCP-1 and insulin, 4 are elevated in obesity 5 and may enhance tumor growth and progression. Adiponectin is an adipocyte-secreted cytokine, or adipokine, that circulates at very high concentrations (3-30 mg/ml). ...
Article
Full-text available
Obesity increases the risk of developing multiple myeloma (MM). Adiponectin is a cytokine produced by adipocytes, but paradoxically decreased in obesity, that has been implicated in MM progression. Herein, we evaluated how prolonged exposure to adiponectin affected the survival of MM cells as well as putative signaling mechanisms. Adiponectin activates protein kinase A (PKA), which leads to decreased AKT activity and increased AMP-activated protein kinase (AMPK) activation. AMPK, in turn, induces cell cycle arrest and apoptosis. Adiponectin-induced apoptosis may be mediated, at least in part, by the PKA/AMPK-dependent decline in the expression of the enzyme acetyl-CoA-carboxylase (ACC), which is essential to lipogenesis. Supplementation with palmitic acid, the preliminary end product of fatty acid synthesis, rescues MM cells from adiponectin-induced apoptosis. Furthermore, 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an ACC inhibitor, exhibited potent antiproliferative effects on MM cells that could also be inhibited by fatty acid supplementation. Thus, adiponectin's ability to reduce survival of MM cells appears to be mediated through its ability to suppress lipogenesis. Our findings suggest that PKA/AMPK pathway activators, or inhibitors of ACC, may be useful adjuvants to treat MM. Moreover, the antimyeloma effect of adiponectin supports the concept that hypoadiponectinemia as occurs in obesity, promotes MM tumor progression.Leukemia accepted article preview online, 20 March 2014; doi:10.1038/leu.2014.112.
... Many risk factors playing an important role in other cancers have not been clearly associated with myeloma [10], and most of the strongest myeloma risk factors still show inconsistent results. Some evidence points to obesity as an important risk factor for myeloma [11,12] whereas other studies have shown non-significant increases in risk [13,14]. Exposure to ionizing radiation, organic solvents and employment in agriculture have also shown conflicting results, and an inherited component has been suggested [15]. ...
Article
Background: Myeloma, one of the most common haematological malignancies worldwide arises in the bone marrow. Incidence rates vary by age and ethnicity but reasons behind these trends are unknown. Treatment of myeloma has changed significantly over recent decades, resulting in longer survival and decreased mortality. Methods: From data supplied by the Ministry of Health, all new registrations of and deaths from myeloma between 1985 and 2016 were extracted. Trends in age-specific rates were assessed using the method of Armitage. Age-standardised rates were calculated, and trends in age-adjusted rates analysed using the Mantel-Haenszel extension chi-square test. Age-adjusted incidence and mortality rate ratios were calculated. Myeloma-specific survival was visualised using Kaplan-Meier curves and multivariable hazard ratios calculated using Cox regression. Results: Between 1985 and 2016, 7826 New Zealanders were registered with myeloma. Over this time the age-specific incidence of myeloma increased significantly for men, who had higher rates than women. Myeloma mortality was highest in Maori men. Men had higher mortality rates than women in all time periods. Since 1995-1999, mortality has decreased in women whereas in men it has declined since about 2000-2004. Survival has increased significantly since 1990 but Maori still have a higher risk of death than non-Maori. Conclusion: The patterns of variation in myeloma incidence, mortality and survival, as well as their trends over time may be used to assist research into the causes and management of myeloma in New Zealand.
... From the studies of FL mortality, one was excluded because it lacked data on mortality in relation to BMI. At the end of the identification process there were 17 applicable studies left with the data on FL incidence (14 for analysis of the influence of OW and OB (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), and 7 for analysis of the influence of PA, from which 4 were previously included (13,15,17,25,(27)(28)(29) as well as 2 studies with data on association between OW and OB and FL mortality (30,31). ...
Article
Full-text available
In the last few years, there has been a growing interest in exploring the association between risk factors such as overweight, obesity and physical activity, and incidence of various cancers. Meta-analysis was performed to investigate the risk ratio of follicular lymphoma incidence and mortality in overweight and obese individuals, and in individuals with a different physical activity levels using the random-effects model. A literature search through September 2016 was performed. Case-control studies accounted for over 2.100 cases and 12.700 controls, whereas cohort studies accounted for over 2.600 cases in cohort of about 3.000.000 individuals. In overweight individuals (body mass index between 25 and 29.99 kg/m 2) risk ratio for the development of follicular lymphoma was 1.03 (0.95-1.11; 95% CI; p = 0.51) and in obese (body mass index ≥ 30 kg/m 2) it was 1.15 (1.01-1.31; 95% CI; p = 0.04) when compared to individuals with normal body mass index (< 25 kg/m 2). The risk ratio of specific follicular lymphoma mortality in overweight was 0.59 (0.38-0.91; 95% CI; p = 0.02), while in obese patients it was 1.08 (0.68-1.71; 95% CI; p = 0.75). In patients with the highest physical activity levels, the risk ratio for follicular lymphoma occurrence was 0.95 (0.75-1.21; 95% CI; p = 0.68) when compared to patients that had the lowest physical activity levels. In summary, our meta-analysis has shown statistically significant direct association between obesity and follicular lymphoma incidence. Acta Medica Medianae 2018;57(4):79-90.
... Since publication of the InterLymph pooled analysis of BMI, where we reported that obesity increased DLBCL risk (1), several studies including cohorts have also found this relationship (25-29) while others have not (11,(30)(31)(32)(33)(34)(35)(36). In summarising published data for DLBCL and obesity, two meta-analyses have noted an increased risk (3,4), the latest including all but the most recent publications (27,28). ...
Article
Full-text available
Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported. Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Obesity (BMI≥30kg m-2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02-1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27-2.94), with a RERI of 0.41 (95%CI -0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma. Copyright © 2015, American Association for Cancer Research.
... Epidemiological studies showed that the risk of BCL is associated with anthropometry measures, lifestyle, viral, environmental and occupational factors (collectively called the exposome). [2][3][4][5][6][7][8] Moreover, in the last two decades, reports from epidemiological studies suggested differences in risks among BCL subtypes for a wide range of risk factors. 2 To better understand the role of risk factors in the occurrence of BCL, it would be preferable to study a large set of lifestyle factors (exposome) in a single study. Few methods are available to comprehensively evaluate the role of specific risk factors with disease. ...
Article
Full-text available
To better understand the role of individual and lifestyle factors in human disease, an exposome‐wide association study was performed to investigate within a single‐study anthropometry measures and lifestyle factors previously associated with B‐cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed‐up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B‐cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
... Although not statistically significant, we found higher risks among blacks, higher education level and higher BMI; these patterns of association are generally consistent with previous studies [4]. For example, increased risks associated with overweight and obesity have been reported in two meta-analyses [28,29] and cohort studies [30][31][32]. It is thought that obesity promotes the growth, survival and migration of malignant plasma cells, potentially via reduced adiponectin and pro-inflammatory cytokines and increased insulin-like growth factors [33][34][35]. ...
Article
We examined lifestyle, occupation, medical history and medication use with multiple myeloma risk in a case-spouse study (481 patients, 351 spouses). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using logistic regression. Compared to spouse controls, cases were more likely to have a family history of multiple myeloma (OR: 2.8,95% CI:1.2,6.4) and smoked cigarettes (OR:1.7,95%CI:1.2,2.5), but less likely to have consumed alcohol (OR:0.6,95%CI:0.4,0.9). Nurse/health practitioners (OR:2.8,95%CI:1.3,6.2) and production workers (OR:3.7,95%CI:1.0,13.7) had significantly increased risks; and some occupations linked to diesel exhaust had elevated, but non-significant, risks. History of herpes simplex (OR:1.7,95%CI:1.2,2.4), shingles (OR:1.7,95%CI:1.1,2.7), sexually transmitted diseases (OR:2.0,95%CI:1.0,3.7), and medication allergies (OR:1.7,95%CI:1.2,2.4) were associated with higher risks. Use of angiotensin-converting enzyme inhibitors, anti-convulsants, antidepressants, statins, and diuretics were associated with reduced risks. Our results are consistent with previous population-based studies, and support the utility of patient databanks and spouse controls as a resource in epidemiologic research.
... A potential interpretation of the association between height and translocations is based on the existing evidence that both height and a higher SES have been associated with an increased risk of NHL [23,24]. In fact, in this study the increased risk of NHL associated with height, in agreement with a previous study of FL [25], was restricted to the t(14;18) ? ...
Article
Full-text available
Purpose: The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established. Methods: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case-control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)(+) as compared to t(14;18)(-) cases. Results: Among incident FL cases, educational level (χ (2) p = 0.021) and height (χ (2) p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31 (95 % CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)(-) cases. Conclusions: These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status.
... Both MGUS and multiple myeloma have been shown to share common risk factors. Certain genetic variations were described in both conditions [12]; obesity was demonstrated as a risk factor for MGUS among women [13] and in myeloma [14][15][16]; diabetes was described as a risk factor for myeloma [17] with insulin-like growth factor 1 as possible promoter of the disease [18], and metformin therapy as a potential protective factor [19]. Autoimmune and chronic inflammatory diseases [20] as well as smoking [21] were also demonstrated in association with both MGUS and myeloma. ...
Article
A number of epidemiologic studies have demonstrated associations between obesity and diabetes and the risk of monoclonal gammopathy of undetermined significance (MGUS). However, since MGUS is an asymptomatic condition we evaluated whether these are true associations or the result of detection-bias. We conducted a nested case-control study using a large primary-care database. Cases were defined as those with incident diagnosis of MGUS. For every case, 4 eligible controls matched on age, sex, practice-site, and duration of follow-up were selected. Exposure variables included obesity and diabetes (including anti-diabetic therapies) as well as other metabolic risk factors. Odds-ratios (ORs) and 95% confidence-intervals (CIs) were estimated using conditional logistic regression. The study included 2,363 MGUS patients and 9,193 matched controls. In the primary analysis, obesity and diabetes were associated with higher MGUS risk with an adjusted ORs of 1.15 (95%CI 1.02-1.29) and 1.30 (95%CI 1.13-1.50), respectively. However, after adjustment to the number of laboratory tests prior to the MGUS diagnosis, there was no association between obesity and diabetes and MGUS risk (ORs of 1.08, 95%CI 0.96-1.22 and 1.08, 95%CI 0.93-1.25 respectively). In an additional analysis of anti-diabetic therapies and MGUS risk, there was a non-significant decrease in MGUS risk among diabetes patients treated with metformin alone compared to subjects without diabetes (OR 0.77, 95%CI 0.56-1.05). In summary, while previously described risk factors for MGUS might be the result of detection bias, metformin should be further evaluated as a possible chemoprevention modality. This article is protected by copyright. All rights reserved.
... Where all controls were included to maximise power, unconditional logistic regression adjusting for the matching variables was used. Confounding was assessed by additionally running an adjusted model; potential confounders were identified as BMI (kg/m 2 ), height (cm), educational level (as a proxy for socioeconomic status), vegetable intake (g/day), dairy intake (g/day), protein intake (g/day), total fat intake (g/day) and alcohol consumption (g/day), based on both a significant (p < 0.05) association with cumulative POP concentration in the total population and a reported association with NHL in the literature [16,17] to ensure biological plausibility for the included confounders. ...
Article
Full-text available
Background Evidence suggests a largely environmental component to non-Hodgkin’s lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined. Methods The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers. ResultsThe exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p < 0.05) in median exposure levels between cases and controls for any of the investigated exposures. However under a multivariate model PCB138, PCB153, HCB and DDE displayed significant inverse trends (Wald test p-value <0.05). Under stratified analyses these were determined to be driven by males and by the Diffuse Large B-Cell Lymphoma subtype. When considering those in the highest levels of exposure (>90th percentile) the association was null for all POPs Conclusion We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL.
... Although the number of MGUS cases overall were small (N = 63), we explored risk factors based on prior studies including: body mass index, 15,[19][20][21] smoking and socioeconomic status (categorized as high versus low by using poverty index ratio o1 versus ⩾ 1). [15][16][17][18] Prevalence of MGUS was not statistically associated with body mass index (data not shown). ...
Article
Full-text available
We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10–49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23–0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62–1.26) compared with whites (0.22%, 95% CI 0.11–0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23–0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40–49 age-group; 3.26% (95% CI 2.04–5.18) versus 0.53% (95% CI 0.20–1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10–19 age-group (both Mexican-American), and in three persons in the 20–29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.
... Long-term smoking has been suggested to increase the risk of lymphoma [28], and within the United States, whites are more likely than African or Asian Americans to develop lymphoma [29]. Some studies have shown an increased risk for lymphoma with high body mass index [30][31][32]. Our study also lacked information on diet, physical activity, or alcohol intake. ...
Article
Full-text available
Purpose: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. Methods: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. Results: For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels declined steeply. Conclusions: This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.
... In one of the largest multicenter studies representing a variety of cancer sites conducted to date, patients receiving a mean of 5.2 and 3.7 days of consecutive filgrastim treatments in 2001 and 2003, respectively, were reported as having FN incidences of 5.3% (31/583) and 7.3% (63/868) [14]. Other retrospective studies as well as randomized trials examining the use of filgrastim and other short-acting G-CSFs for breast cancer patients receiving adjuvant or neoadjuvant chemotherapy reported incidences of FN in their cohorts ranging from 9.1% to 18% [15][16][17]. One study with similar findings to our own found FN incidence among Stage II to IV breast cancer patients treated with filgrastim (the majority receiving at least nine injections) to be 2.38% [18]. ...
Article
Full-text available
Background Filgrastim is used in the setting of chemotherapy-induced neutropenia to stimulate recovery of bone marrow, which allows for further chemotherapy administration without delay. The recommended dose is 5 ug/kg. The commercially available vials of the drug come in two strengths; 300 ug and 480 ug. Due to these limitations in dosage formulations, it is a frequent occurrence to administer a lower dosage to patients weighing more than 60 kg, in whom the ideal dose would have been more than 300 ug but less than 480 ug. It is also a frequent practice to administer the drug for two consecutive days as it often leads to adequate response that will render patients eligible for their next cycle administration. Objective To determine whether a course of 300 ug of filgrastim administered daily for two consecutive days was as successful at reducing chemotherapy-induced neutropenia-related complications in patients with a higher weight (>60 kg) and hence receiving suboptimal dose as compared to those with weight less than 60 kg who are receiving the recommended dose. Methods We identified 91 patients from our facility with chemotherapy-induced neutropenia treated with 300 ug of filgrastim daily for two consecutive days, and we separated them into low, medium, and high weight groups. Multivariate logistic regression models examined correlations between outcomes (e.g., increases in absolute neutrophil count) and predictors (e.g., weight groups). Results The vast majority of encounters demonstrated rises in white blood cell (WBC) and absolute neutrophil count (ANC). Infection rates were not significantly different between low and medium weight groups (5% vs 0%; p = 0.1658), but the high weight group’s infection rate was significantly higher than the medium weight group (5% vs 33%; p = 0.001). The high weight group did have an increased rate of febrile neutropenia as compared to medium and low weight groups, but these differences were not significant. Incidences of chemotherapy delay and dose reduction were comparable across the three weight groups. Limitations Retrospective study, small sample size, heterogeneous cancer sites and different chemotherapy regimens administered limit generalizability of findings. Conclusion Patients with weights <85 kg receiving a two-day course of 300 ug of filgrastim have similar neutropenia-related complication rates with a potential percent cost-savings of roughly 43%.
... but no significant association was seen with higher BMI (BMI ≥28.7 kg/m 2 ) (RR 1.52; 95% CI 0.92-2.51) [24]. Similarly, several other studies showed no significant association between BMI and MM risk [25][26][27][28]. ...
Article
Multiple myeloma (MM) remains an incurable plasma cell malignancy. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes, poor nutrition, many of which are modifiable, have been linked to the pathogenesis of numerous neoplasms including MM. In this article, we provide a detailed summary of what is known about the impact of obesity on the pathogenesis of MM, its influence on outcomes in MM patients, and discuss potential mechanisms through which obesity is postulated to influence MM risk and prognosis. Along with advancements in treatment modalities to improve survival in MM patients, focused efforts are needed to prevent or intercept MM at its earliest stages. The consolidated findings presented in this review highlight the need for clinical trials to assess if lifestyle modifications can reduce the incidence and improve outcomes of MM in high-risk populations. Data generated from such studies can help formulate evidence-based lifestyle recommendations for the prevention and control of MM.
Article
We conducted a meta-analysis of prospective studies to summarise the epidemiologic evidence regarding the association of body mass index (BMI) with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) incidence and NHL mortality. Pertinent studies were identified by searching PubMed (1966-May 2011) and the reference lists of retrieved articles. For each study, we estimated a relative risk (RR) for a 5 kg/m(2) increase in BMI. A random-effects model was used to combine the RR estimates from individual studies. The summary RRs for a 5 kg/m(2) increase in BMI were 1.07 (95% confidence intervals (CI), 1.04-1.10) for NHL incidence (16 studies, n=17,291 cases) and 1.14 (95% CI, 1.04-1.26) for NHL mortality (five studies, n=3407 cases). BMI was significantly positively associated with risk of diffuse large B-cell lymphoma (RR, 1.13; 95% CI, 1.02-1.26), but not other NHL subtypes. The difference in risk estimates for subtypes was not statistically significant (P=0.10). There was evidence of a nonlinear association between BMI and HL (P for nonlinearity=0.01) (five studies, n=1557 cases). The summary RRs of HL were 0.97 (95% CI, 0.85-1.12) for overweight and 1.41 (95% CI, 1.14-1.75) for obesity. These results indicate that BMI is positively associated with risk of NHL and HL as well as with NHL mortality.
Article
Full-text available
Incidence rates of non-Hodgkin's lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20th century, but little is known about its etiology. Obesity is associated with impaired immune function through which it may influence the risk of NHL; other factors reflecting energy homeostasis (height, abdominal adiposity, and physical activity) may also be involved. We examined the association of anthropometric factors and physical activity with risk of NHL and its major subtypes in a large cohort of women aged 50-79 years old who were enrolled at 40 clinical centers in the United States between 1993 and 1998. Over a mean follow-up period of 11 years, 1123 cases of NHL were identified among 158,975 women. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Height at baseline was positively associated with risk of all NHL and with that of diffuse large B-cell lymphoma (HRs(q4vs.q1) 1.19, 95% CI 1.00-1.43 and 1.43, 95% CI 1.01-2.03, respectively). Measures of obesity and abdominal adiposity at baseline were not associated with risk. Hazard ratios for NHL were increased for women in the highest quartile of weight and body mass index at age 18 (HRs(q4vs.q1) 1.29, 95% CI 1.01-1.65 and 1.27, 95% CI 1.01-1.59, respectively). Some measures of recreational physical activity were modestly associated with increased risk of NHL overall, but there were no clear associations with specific subtypes. Our findings regarding anthropometric measures are consistent with those of several previous reports, suggesting that early life influences on growth and immune function may influence the risk of NHL later in life.
Article
Obesity may increase the risk of neoplasia, including that of the lymphohematopoietic system. In a large Taiwanese cohort, we have evaluated whether body fat and its distribution is associated with non-Hodgkin's lymphoma (NHL) and leukemia mortalities. During 1997-2007 in Taiwan, 383,956 subjects aged 19-98 years without any cancer history were obtained through a health screening center and followed up for a median of 7.2 years. Unit records were linked to the national death registry; ICD-9 codes were used to identify 143 NHL and 73 leukemia deaths. Objectively, height, weight, and waist circumference data were measured to calculate body mass index (BMI) and central obesity status. Based on World Health Organization criteria modified for Asia and Taiwan, BMI was classified to <18.5, 18.5-23.9, 24-26.9, and ≥ 27 kg/m(2). Waist circumference ≥ 90 cm in men and ≥ 80 cm in women was defined as central obesity. Cox proportional hazard regression models were adjusted for possible confounders including gender, age, education, smoking status, alcohol consumption, physical activity, and clinic location. BMI was not associated with NHL deaths, although the trend was significant, but central obesity with adjustment was (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.27-2.75) compared with non-centrally obese subjects. BMI, but not central obesity, was associated with leukemia mortality (HR = 1.93, 95% CI = 1.00-3.75). An increased risk for NHL with increased abdominal fatness and more so with lower BMI is apparent in Taiwanese; this may indicate that metabolically localized and proinflammatory fat is important. For leukemia, where most is myeloid leukemia, increased general fatness is evidently a risk with Taiwanese ethnicity.
Article
The present study aims to identify occupational exposures associated with incidence of multiple myeloma (MM). A population-based case-control study of MM (ICD-9 203) was conducted among Canadian males, with a total of 342 cases and 1506 controls contributing to the final analyses. Conditional logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI), stratifying by age groups and province of residence. Based on the most parsimonious multivariable model, the following variables were significantly associated with an increased incidence of MM: exposure to coal dust (OR 1.7, 95% CI 1.2-2.4), long-held occupations as a carpenter (OR 3.2, 95% CI 1.4-7.1) or a machinist (OR 2.4, 95% CI 1.0-5.8); and immediate family member having been previously diagnosed with certain cancers (OR 1.4, 95% CI 1.1-1.8). In this study of Canadian men, a higher risk of MM may be associated with exposure to coal dust, long-held occupations as a carpenter or machinist, and a positive family history of cancer.
Article
Full-text available
Bierman and Rea outlined some corrections and offered further information regarding the lighting sources described in our article. We welcome their comments and respond to each point as follows. First and second, Bierman et al. stated that high-intensity discharge (HID) and fluorescent lamps of similar wattage are approximately equal in terms of efficiency and that light-emitting diode (LED) lamps appear far brighter than fluorescent lamps. Although we welcome such advice, it was beyond the scope of our study to determine the particular characteristics of HID or LED lamps required in a work environment using fluorescent lamps to produce the required concentration and visual acuity. (Am J Public Health. Published online ahead of print June 14, 2012: e1. doi:10.2105/AJPH.2012.300754).
Multiple myelomas are a less frequent cancer site among both sexes. On a worldwide scale, it is estimated that about 86 000 incident cases occur annually, accounting for about 0.8% of all new cancer cases. About 63 000 subjects are reported to die from the disease each year, accounting for 0.9% of all cancer deaths. Geographically, the frequency is very unevenly distributed in the world with the highest incidence in the industrialised regions of Australia / New Zealand, Europe and North America. Incidence and mortality seem to be stable in Asian countries and to increase slowly over the decades among whites in the western countries. The etiology is poorly understood. This depends partly upon the fact that the risk factors which play a major role for malignant diseases in general, such as tobacco consumption and diet have not been found strongly involved into multiple myeloma etiology. Nevertheless, some consistency seems to be in the findings about a risk elevation with obesity and a slightly decreased risk with high fruit consumption. Despite some contradicting results, indications to a role of ionising radiation persist. Finally, infections with HIV and hepatitis C virus appear related to an elevated multiple myeloma risk. Currently, large efforts are undertaken to unravel the etiology of malignant lymphoma including those of multiple myeloma.
Chapter
Multiple myeloma, a plasma cell tumor arising in the bone marrow, is a rare cancer with an elusive etiology. In the USA, myeloma is estimated to account for approximately 1.3 % of all diagnosed cancers and 1.9 % of all cancer deaths [1]. According to estimates provided by the American Cancer Society, approximately 11,170 men and 9,010 women were expected to develop multiple myeloma, and 5,760 men and 4,890 women were expected to die from myeloma in the USA during 2010 [1]. The lifetime risk of being diagnosed with myeloma in the USA is 1.09 % for black men, 0.68 % for white men, 1.08 % for black women, and 0.51 % for white women [2].
Article
ABSTRACT Results from epidemiologic studies examining associations between body size and risk of non-Hodgkin lymphoma (NHL) are inconsistent and etiology may vary by histologic subtypes of disease. Using Cox proportional hazards regression, multivariable relative risks (RR) and 95% confidence intervals (CI) were computed for associations of body mass index (BMI) and height with NHL in the prospective American Cancer Society Cancer Prevention Study-II Nutrition Cohort. From 1992-2007, 2,074 incident NHL cases were identified among 152,423 men and women. Obese individuals (BMI ≥ 30kg/m(2)) had 23% higher incidence of NHL (95% CI 1.08-1.40) compared to normal weight (BMI 18.5-<25kg/m(2)). Height was positively associated with NHL (RR=1.25, 95% CI 1.10-1.43, sex-specific quintile 5 vs. 1). BMI associations were strongest for diffuse large B-cell lymphoma; height was most strongly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma and to a lesser extent with multiple myeloma. These findings provide further evidence that body size may play a role in the etiology of NHL, which is of public health importance given the rapid rise in obesity worldwide.
Article
Purpose: Overweight and obesity have been suggested as a risk factor for leukemia. Impaired immune function associated with obesity, increased insulin-like growth factor-I activity and stimulating effects of leptin suggest a possible biological link between anthropometric measures and leukemia. However, evidence from epidemiological studies has been inconsistent. We examined the potential association between prospective measurements of body size and risk of leukemia among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: During follow-up (mean = 11.52 years, standard deviation = 2.63), 671 leukemia (lymphoid leukemia = 50.1 %, myeloid leukemia = 43.2 %) cases were identified. Anthropometric measures including weight, height, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-hip ratio (WHR) were measured. Cox proportional hazard models were used to explore the association between anthropometric measures and risk of leukemia. Results: No associations were observed between anthropometric measures and total leukemia, and lymphoid leukemia. Risk of myeloid leukemia significantly increased for higher categories of BMI and WC among women. Analyses by subtype of myeloid leukemia showed an increased risk of acute myeloid leukemia (AML) for higher categories of WHR among women. This association seemed to be reversed for chronic myeloid leukemia. No association between anthropometric measures and myeloid leukemia were observed among men except an increased risk of AML with height. Conclusion: The study showed no associations between anthropometric measures and total leukemia, and lymphoid leukemia among men and women. A possible association between BMI as general obesity and WC as abdominal obesity and increased risk of myeloid leukemia among women were observed.
Article
Epigenetic alterations represent a key cancer hallmark, even in hematologic malignancies (HMs) or blood cancers, whose clinical features display a high inter-individual variability. Evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-based, clinical and experimental studies, we hypothesize that factors associated with risk for developing a HM, such as metabolic syndrome and chronic inflammation, trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Among others, signaling pathways associated with such risk factors include pro-inflammatory nuclear factor κB (NF-κB), and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways, which include signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/ mitogen-activated protein kinases (MAPKs) /extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt / mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.
Article
Full-text available
Despite tremendous advances in treatments for myeloma in the past decade, the disease remains incurable in the majority of patients. Here, we review recent data demonstrating an association between obesity and increased risk of myeloma development. This may be due to the pro-inflammatory cytokine profile caused by obesity. Currently, there are no screening or prevention strategies for myeloma, but we propose that obesity-associated inflammatory pathways, or obesity itself, may be amenable to intervention, thereby preventing the transition from pre-malignancy to myeloma. In addition, we suggest that the morbidity, mortality and the significant costs associated with myeloma treatment could be reduced by addressing modifiable risk factors, and that research efforts should explore this novel hypothesis.Bone Marrow Transplantation advance online publication, 12 May 2014; doi:10.1038/bmt.2014.71.
Article
Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma, accounting for 30-40% of newly diagnosed cases. Obesity is a well-defined risk factor for DLBCL. However, the impact of BMI (Body mass index) on DLBCL prognosis is controversial. Recent studies suggest that skeletal muscle wasting (sarcopenia) or loss of fat mass can be detected by computed tomography (CT) images and is useful for predicting the clinical outcome in several types of cancer including DLBCL. Several hypotheses have been proposed to explain the differences in DLBCL outcomes according to BMI or weight that include tolerance to treatment, inflammatory background, and chemotherapy or rituximab metabolism. In this review, we summarize the available literature, addressing the impact and physiopathological relevance of simple anthropometric tools including BMI and tissue distribution measurements. We also discuss their relationship with other nutritional parameters and their potential role in the management of DLBCL patients.
Chapter
Evidence from epidemiologic studies suggests that excess body fat may influence risk for hematologic malignancies including multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), and leukemia. Mechanisms related to adiposity and its effects on energy metabolism, immune function, and the endocrine environment are thought to act in the pathways that give rise to these malignancies. The research literature on this topic, however, is as yet insufficient for conclusion, and much more data may be required before any association between excess weight and this diverse group of cancers can be reliably established. Existing data to support such an association are compelling nonetheless and, given the extent and magnitude of the obesity epidemic and its implications for human health, deserve an exhaustive scientific evaluation. The aims of this chapter are to summarize the current state of research on obesity and hematologic malignancies in adults and children, and provide a focus for future study in this area.
Chapter
Multiple myeloma (MM) is a plasma B-cell malignancy that is characterized by the presence of clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in blood or urine, and organ dysfunction. It accounts for 10% of hematological malignancies and approximately 1% of all cancers in the USA. Several etiologic agents are associated with its development. Notably, obesity is consistently associated with increased risk and drives mechanistic pathways important in its development. In addition to age, black or African American heritage is a consistent risk factor as is male gender. Epidemiologic evidence on causes and biologic pathways supporting the obesity relation are presented. Diagnosis and treatment of MM patients are considered in the context of obesity as a cause with potential impact on treatment and outcomes among those with disease.
Article
Background: Multiple myeloma (MM) risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with MM. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric MM risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 MM cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, MM risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m(2) increase in BMI (odds ratio [OR]=1.09, 95% confidence interval [CI]= 1.04-1.14; p=0.007). We observed significant heterogeneity by study design (p=0.04), noting the BMI-MM association only for population-based studies (p-trend=0.0003). Young adult BMI was also positively associated with MM (per 5-kg/m(2); OR=1.2, 95% CI=1.1-1.3; p=0.0002). Further, we observed strong evidence of interaction between younger and usual adult BMI (p-interaction <0.0001); we noted statistically significant associations with MM for persons overweight (25-<30 kg/m(2)) or obese (30+ kg/m(2)) in both younger and usual adulthood (v. individuals consistently <25 kg/m(2)), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in MM risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase MM risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of MM prevention.
Article
Full-text available
Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHL), HL, and multiple myeloma, occur at much lower rates in Asians than other racial/ethnic groups in the United States. It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status. We obtained data about all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from U.S. Census data. Although incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than U.S.-born Asians with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower SES neighborhoods than those living elsewhere. These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL. Studying specific lymphoid malignancies in U.S. Asians may provide valuable insight toward understanding their environmental causes.
Article
Full-text available
Food composition tables were studied from nine European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC): Denmark, France, Germany, Greece, Great Britain, Italy, The Netherlands, Spain and Sweden. They were compared from the point view of availability, definition, analytical methods, and mode of expression of the nutrients of interest for EPIC, and it was seen that most of the nutrients in the tables are analysed and expressed in a compatible way. For some nutrients, however, common methods and definitions (folate, dietary fibre), or modes of expression (energy, protein, carbohydrates, carotenes, vitamin A and E) have not yet been agreed upon, so values are not comparable. For vitamin C a wide range of values are found due to the high natural variation in foods. For compiled tables, an additional problem is the use of several sources which may mean that the nutritional values are not comparable within the same table; and these values cannot be converted if the source is not stated. In addition, some tables were compiled using food composition values produced over 20 years ago with outdated analytical methods. In view of the inconsistent values for some nutrients and due to the large amount of foods reported within EPIC, it was concluded that standardised food composition tables have to be developed for the nine European countries involved in EPIC in order to provide comparable nutrient intake data.
Article
Full-text available
To examine in detail the cause specific associations between height and mortality. A prospective cohort study with an 18 year mortality follow up. The Whitehall study of 18,403 men in the civil service in London examined between 1967 and 1969 aged 40-64 and followed up for mortality until the end of January 1987. There was considerable variation in the strength of height-mortality association by cause. Respiratory disease showed the strongest inverse association, cardiovascular disease a moderate effect, and all neoplasms virtually no effect. Adjustment for age and civil service grade reduced the strength of these associations slightly, but had no impact on the heterogeneous pattern by cause (chi 2 3df p < 0.001). The height-mortality association declined with the length of follow up. By 15+ years, the only appreciable height affect was for respiratory disease mortality. The attenuation of the height-mortality association with length of follow up might be explained by differential height reduction before entry that was greatest for people who were already ill, and hence at greatest risk of dying. The cause specific variation in the height-mortality association lends little support to the contention that impaired growth in childhood is a marker of general susceptibility to disease in adulthood.
Article
Full-text available
The most consistent result of epidemiological studies on diet and cancer is that a diet rich in vegetables, fruit and, more generally, in plant foods is associated with a reduced risk of cancer at several anatomical sites. Epidemiological studies have been less consistent regarding the putative increase in risk related to consumption of fat or meat. In addition it has not been possible to identify clearly the biological role of specific nutrients or non-nutrient food components in the prevention or causation of cancer. Limitations in the precision and validity of traditional dietary intake measurements and limited use of biomarkers combined with narrow ranges of variations in dietary habits within single populations, have been the main reasons for the limited success in identifying more specific diet and cancer links. EPIC is a multi-centre prospective cohort study designed to investigate the relation between diet, nutritional and metabolic characteristics, various lifestyle factors and the risk of cancer. The study is based in 22 collaborating centres in nine European countries and includes populations characterized by large variations in dietary habits and cancer risk. Data are collected on diet, physical activity, sexual maturation and reproductive history, lifetime consumption of alcohol and tobacco, previous and current illnesses and current medication. Following a common protocol and using identical equipment, blood samples are collected, aliquoted into plasma, serum, white blood cells and erythrocytes, and stored in liquid nitrogen at -196 degrees C for future laboratory analyses on cancer cases and matched healthy controls. Anthropometric measurements are taken according to a standard protocol. It is planned to include around 400,000 middle-aged men and women. The collection of questionnaire data, anthropometric measurements and blood samples is under way. Almost 340,000 subjects had been included in the study by mid-1996, and recruitment is expected to be almost complete by 1997. Follow-up for cancer incidence and total mortality has started and it is expected that about 23000 cancer cases will be identified during the first 10 years of follow-up.
Article
Full-text available
Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma. We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88 410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P<.05. Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend =.42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% CI = 1.1-4.4; P for trend =.002). Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend =.01). Higher intake of red meat cooked by broiling or barbecuing-but not by roasting, pan-frying, or boiling or stewing-was associated with an increase in risk that was not statistically significant. Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma. These relationships and their potential mechanisms deserve further examination.
Article
Full-text available
The immunological processes involved in the collaborative defence of organisms are affected by nutritional status. Thus, a positive chronic imbalance between energy intake and expenditure leads to situations of obesity, which may influence unspecific and specific immune responses mediated by humoral and cell mediated mechanisms. Furthermore, several lines of evidence have supported a link between adipose tissue and immunocompetent cells. This interaction is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. However, limited and often controversial information exist comparing immunity in obese and non-obese subjects as well as about the cellular and molecular mechanisms implicated. In general terms, clinical and epidemiological data support the evidence that the incidence and severity of specific types of infectious illnesses are higher in obese persons as compared to lean individuals together with the occurrence of poor antibody responses to antigens in overweight subjects. Leptin might play a key role in linking nutritional status with T-cell function. The complexities and heterogeneity of the host defences concerning the immune response in different nutritional circumstances affecting the energy balance require an integral study of the immunocompetent cells, their subsets and products as well as specific and unspecific inducer/regulator systems. In this context, more research is needed to clarify the clinical implications of the alterations induced by obesity on the immune function.
Article
Full-text available
To describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A cross-sectional analysis of baseline data of a European prospective cohort study. This analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a 'health-conscious' group. The analysis was restricted to 83 178 men and 163 851 women aged 50-64 years, this group being represented in all centres. Anthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the 'health-conscious' group (UK), anthropometric measures were predicted from self-reports. Except in the 'health-conscious' group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m-2. The prevalence of obesity (BMI> or =30 kg m(-2)) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (>25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (<10%) in the French centres and the 'health-conscious' group (UK). The prevalence of a large waist circumference or a high waist-to-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands). Anthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.
Article
Full-text available
The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
Article
Full-text available
A population-based case-control study of lymphomas in England collected height and weight details from 699 non-Hodgkin's lymphoma (NHL) cases and 914 controls. Obesity, defined as a body mass index (BMI) over 30 kg m(-2) at five years before diagnosis,, was associated with an increased risk of NHL (OR = 1.5, 95% CI 1.1-2.1). The excess was most pronounced for diffuse large B-cell lymphoma (OR = 1.9, 95% CI 1.3-2.8). Genetic variants in the leptin (LEP 19G > A, LEP -2548G > A) and leptin receptor genes (LEPR 223Q > R), previously shown to modulate NHL risk, as well as a polymorphism in the energy regulatory gene adiponectin (APM1 276G>T), were investigated. Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR = 0.7, 95% CI 0.5-1.0) and increased with LEP -2548GA (OR = 1.3, 95% CI 1.0-1.7) and -2548AA (OR = 1.4, 95% CI 1.0-1.9), particularly for follicular lymphoma. These genetic findings, which were independent of BMI, were stronger for men than women.
Article
Full-text available
The authors conducted a population-based case-control study of 1,030 cases with histologically confirmed, incident non-Hodgkin's lymphoma (NHL) and 3,106 controls to assess the impact of recreational physical activity, obesity, and energy intake on NHL risk in Canada from 1994 to 1997. Compared with those for subjects in the lowest quartiles of total recreational physical activity, multivariable-adjusted odds ratios for subjects in the highest quartile were 0.79 (95% confidence interval (CI): 0.59, 1.05) for men and 0.59 (95% CI: 0.42, 0.81) for women. Obesity (body mass index ≥30 kg/m2) was associated with odds ratios of 1.59 (95% CI: 1.18, 2.12) for men and 1.36 (95% CI: 1.00, 1.84) for women. For men and women with a lifetime maximum body mass index of ≥30 kg/m2, respective odds ratios were 1.55 (95% CI: 1.16, 2.06) and 1.10 (95% CI: 0.83, 1.46). For men and women in the highest quartiles of calorie intake, respective odds ratios were 1.95 (95% CI: 1.45, 2.62) and 1.13 (95% CI: 0.84, 1.52). Some differences were found between histologic subtypes of NHL for these associations. This study suggests that recreational physical activity decreases NHL risk, while obesity and excess calorie intake increase it. More studies are needed to confirm these results, especially the differences between histologic subtypes.
Article
Full-text available
Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL, self-reported anthropometric data on weight and height from over 10,000 cases of NHL and 16,000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m(-2) or more, was not associated with NHL overall (pooled OR = 1.00, 95% confidence interval (CI) 0.70-1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR = 1.80, 95% CI 1.24-2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25-29.9 kg m(-2)) and obese (BMI 30-39.9 kg m(-2)), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI < 18.5 kg m(-2)). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m(-2) rise in BMI above 18.5 kg m(-2). BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR = 1.19, 95% CI 1.06-1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation.
Article
BACKGROUND—The annual incidence of non-Hodgkin's lymphomas (NHL) is increasing by 3%-4% in different parts of the developed world. Excesses of NHL have been observed in populations exposed to immunosuppressants and to HIV, but these causes do not explain the increasing trends. It is suggested that delayed infection could explain NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. METHODS—In a population-based study on 1388 patients with NHL, 354 with Hodgkin's disease (HD) and 1718 healthy controls, the age of first occurrence of bacterial and viral diseases was investigated. Clinical records were perused in one centre to check the anamnestic data. FINDINGS—The age of occurrence of bacterial and viral diseases was significantly higher among NHL patients than in the controls. The association between later age at first bacterial or viral disease was limited to small families (OR= 1.95; 95% confidence intervals 1.26, 3.00, for age 4-8 at first infection; OR=1.91; 1.19, 3.06, for age 9+, compared with less than 4). The association was more obvious for bacterial diseases (possibly for the lower degree of misclassification). High grade lymphomas showed the strongest association. The later age of occurrence of bacterial or viral diseases in NHL patients is consistent with a higher incidence of lymphomas observed in higher social groups. No clear association was found between HD and age at first bacterial or viral diseases. INTERPRETATION—It is proposed that delayed infection could explain the increasing NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. The model of delayed infection has been proposed also to explain increasing prevalence rates of asthma.
Article
Objective: We evaluated the relation between obesity and the risks for various forms of cancer. Methods: In a population-based cohort of 28,129 hospital patients (8165 men, 19,964 women) with any discharge diagnosis of obesity (9557 only diagnosis, 5266 primary, 13,306 secondary) during 1965–1993, cancer incidence was ascertained through 1993 by record linkage to the nationwide Swedish Cancer Registry. Cancer risk was estimated using the standardized incidence ratio (SIR, with 95% confidence interval), which is the ratio of the observed number of cancers to that expected. Results: Overall, a 33% excess incidence of cancer was seen in obese persons, 25% in men and 37% in women. Significant risk elevations were observed for cancers of the small intestine (SIR = 2.8; 95% CI 1.6–4.5), colon (1.3; 1.1–1.5), gallbladder (1.6; 1.1–2.3), pancreas (1.5; 1.1–1.9), larynx (2.1; 1.1–3.5), renal parenchyma (2.3; 1.8–2.8), bladder (1.2; 1.0–1.6), cervix uteri (1.4; 1.1–1.9), endometrium (2.9; 2.5–3.4), ovary (1.2; 1.1–1.5), brain (1.5; 1.2–1.9), and connective tissue (1.9; 1.1–3.0), and for lymphomas (1.4; 1.0–1.7), with higher risk observed for Hodgkin's disease only in men (3.3; 1.4–6.5) and for non-Hodgkin's lymphoma only in women (1.6; 1.2–2.1). The association of obesity with risk of breast, prostate and pancreas cancers was modified by age. Conclusions: Obesity is associated with more forms of cancer than previously reported.
Article
A cohort of 43 965 obese persons was accrued on the basis of discharge registrations from Danish hospitals, and incidence of cancer in the cohort was compared to that in the Danish population as a whole using indirect standardisation for age and period. Increased incidence was observed for cancer of the uterine corpus independently of age [114 cases, relative risk (RR) = 2.0, confidence interval 1.6–2.4], and for breast cancer in women above the age of 70 (133 cases, RR = 1.2). These findings are consistent with previous studies. In younger women, breast cancer occurred less frequently and ovarian cancer occurred more frequently than expected. Increased incidence was observed for cancers of the oesophagus (26 cases, RR = 1.9) and the liver (58 cases, RR = 1.9), probably reflecting an increased prevalence of excessive alcohol consumption in the cohort. Increased incidence was furthermore observed for cancers of the pancreas (101 cases, RR = 1.7), the prostate (96 cases, RR = 1.3) and the colon (195 cases, RR = 1.2), which may indicate the existence of risk factors which are common to obesity and to these cancers, for example, dietary habits. Kidney cancer was increased in women only. Overall, the incidence of cancer was increased by 16% in the cohort. The results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge. Selection bias is, therefore, not likely to have influenced the results.
Article
College health records of 50,000 male alumni of Harvard University (Cambridge, Mass.) and the University of Pennsylvania (Philadelphia, Pa.) were examined for characteristics that were predictive of risk of fatal lymphaden, blood, and skin cancers. Among these alumni, 45 men with Hodgkin's disease, 89 with non-Hodgkin's malignant lymphoma, 45 with malignant melanoma, 27 with lymphatic leukemia, 41 with myeloid leukemia, and 30 with other and unspecified leukemia died from their disease in 1.71 million person-years of observation. Men grouped according to the type of cancers they had, identified from death certificates, were contrasted with four times as many surviving classmates in terms of potential predictive characteristics. Relative risks of these six cancers may be grouped by predictive characteristics in youth as follows: (1) History of common contagious diseases of childhood was predictive of a lower risk of Hodgkin's disease and lymphatic leukemia, but varicella indicated increased risk of other malignant lymphomas and unspecified leukemia. (2) Tonsillectomy was associated with higher risk of unspecified leukemia. (3) Obesity was a predictive factor of excess risk of Hodgkin's disease, whereas leannesss was associated with higher risk of other lymphomas. (4) Both coffee drinking and heavy cigarette smoking pointed to higher risk of Hodgkin's disease, myeloid leukemia, and lymphatic leukemia. (5) Outdoor environmental exposure indicated increased risk of malignant melanoma. In the tendencies noted, Hodgkin's disease and lymphatic leukemia had parallel predictive factors that were opposite to those of non-hodgkin's malignant lymphoma, myeloid leukemia, and unspecified leukemias. Malignant melanoma shared none of these predictive characteristics. These findings are presented as clues deserving further exploration for any etiologic significance they may hold for lymphaden and blood cancers.
Article
We concluded a study on 208 cases of non-Hodgkin's lymphoma and 401 controls in the North-East of Italy in order to investigate the role of indicators of socio-economic status, personal habits, past history of various disorders and medical treatments potentially affecting the immune system, and occupational exposures in the aetiology of such neoplasia. None of the several investigated characteristics appeared to be a strong determinant, i.e. relative risk, RR greater than 2.0, of non-Hodgkin's lymphoma. Cases and controls appeared to be very similar as regards education, main life-time occupation and alcohol consumption. Positive associations, however, emerged with chronic infectious diseases, mainly tuberculosis and malaria (RR = 1.8, 95% confidence interval, CI: 1.1-2.9). Non significantly increased risks were also found for smoking habit (RR ever vs never smokers = 1.5, 95% CI: 1.0-2.3), episodes of herpes zoster infection (RR = 1.4; 95% CI: 0.7-2.6) and occupation in chemical and petrochemical industries (RR = 1.6; 95% CI: 0.9-3.1, and 1.8; 95% CI: 0.9-3.8, respectively). Conversely, farming as well as specific exposure to herbicides and pesticides did not seem to affect the risk of non-Hodgkin's lymphoma in the present investigation.
Article
This supplement contains the results from studies in the eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Each collaborating centre has assessed the relative validity and reproducibility of the dietary assessment method being used in their centre. One study has also looked at the relative validity of a measure of physical activity, and another study presents the results on an inter-observer study of anthropometric measures. The paper by Kaaks 1 discusses some fundamental assumptions (particularly the statistical independence of random measurement errors between different measurements) that govern the design and analysis of the preliminary validity studies of the pilot phase of the EPIC project. He presents the rationale for conducting additional ‘calibration’ studies on representative subsamples of participants in the main cohort studies, and the way the results from the calibration study in each centre may be used to allow the data to be pooled and used to explore the relationship between a wider range of intake and cancer risk. The paper by Kaaks, Slimani and Riboli 2 gives an overview and summary of the
Article
Three methods for measuring time spent in daily physical activity (PA) were compared during a 21-d period among 83 adults (38 men and 45 women). Each day, participants wore a Computer Science and Applications, Inc. (CSA) monitor and completed a 1-page, 48-item PA log that reflected time spent in household, occupational, transportation, sport, conditioning, and leisure activities. Once a week, participants also completed a telephone survey to identify the number of minutes spent each week in nonoccupational walking and in moderate intensity and hard/very hard-intensity PA. Data were analyzed using descriptive statistics and Spearman rank-order correlations. Three equations developed to compute CSA cut points for moderate and hard/very hard PA were also compared with the PA logs and PA survey. There was modest to good agreement for the time spent in different PA intensity categories between the three CSA cut point methods (r = 0.43-0.94, P < 0.001). Correlations between the CSA and PA logs ranged from r = 0.22 to r = 0.36, depending on the comparisons. Correlations between the survey items and PA logs were r = 0.26-0.54 (P < 0.01) for moderate and walking activities and r < 0.09 (P > 0.05) for hard/very hard activities. Correlations between the survey items and the CSA min per day varied according to the method used to compute the CSA intensity cut points. The results were consistent with findings from other PA validation studies that show motion sensors, PA logs, and surveys reflect PA; however, these methods do not always provide similar estimates of the time spent in resting/light, moderate, or hard/very hard PA.
Article
Recently there have been substantial improvements in our understanding of the biology of myeloma. These findings have important implications for aetiological studies aimed at defining the causative factors for myeloma. Myeloma is closely related to monoclonal gammopathy of unknown significance (MGUS), which is now recognized to be very common in the older population. The epidemiology of these conditions is presented and discussed in the context of the genetic factors governing both the risk of developing MGUS or of transformation to myeloma. Biological studies support a role for aberrant class switch recombination early in the natural history of myeloma suggesting that factors in the environment may interact with this mechanism to increase myeloma risk. Case-control and cohort studies have identified several known and suspected environmental exposures. These exposures include high doses of ionizing radiation, and occupational exposure in the farming and petrochemical industries. The data supporting these associations are presented and discussed in the context of the molecular mechanisms underlying these exposures. In particular DNA damage occurring as a consequence could readily interact with the class switch recombination process to increase the risk of chromosomal translocations, oncogene deregulation and malignant transformation. A further hypothesis, which has been extensively investigated, is the role of chronic immune/antigenic stimulation and the risk of myeloma. This concept is difficult to explain in the context of our current immunological concepts. The data supporting the association and how molecular epidemiological studies using genetic variants in cytokine genes are allowing us to revisit this concept are discussed in detail.
Article
The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Article
The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.
Article
The incidence of non-Hodgkin's lymphoma (NHL) has doubled over the past two decades in the US and most other westernized countries. While improved cancer reporting, changes in lymphoma classification, and increases in AIDS-associated lymphomas have contributed to the startling escalation of disease incidence, these factors are estimated to account for only about 50% of the increase in observed incidence. The elucidation of etiologic factors and their mechanistic role in the pathogenesis of this malignancy are critical to advancements in disease prevention and treatment. Current evidence suggests that factors/conditions that precipitate either chronic antigenic stimulation or immunosuppression may provide a preferential milieu for development of NHL. High rates of lymphoma have been observed among individuals with autoimmune disease, organ transplants, and primary or acquired immunodeficiencies. Ultraviolet radiation, previously demonstrated to have an immunosuppressive effect, has also been suggested as a possible risk factor for NHL. Several pathogens have been linked to the risk of lymphoma, including Epstein-Barr virus, human immunodeficiency virus, human T-cell lymphotropic virus-1, Helicobacter pylori, hepatitis C, and simian virus 40. Whether these microbes are responsible for specific genetic mutations that initiate tumor growth, antigenic stimulation leading to B-cell proliferation, and increased potential of random cell replication errors, or immunosuppression, which thereby promotes tumor growth, has not been clearly delineated. Other exogenous factors which have been implicated in lymphomagenesis are chemicals and agricultural exposures, hair dyes, and blood transfusions. We must build on our current knowledge regarding the etiology of NHL in order that prevention, treatment, and ultimately, cure of this malignancy becomes a reality.
Article
Animal and human studies have suggested that antidepressant medications may be associated with several cancers. The authors evaluated the association between antidepressant medication use and the risk of non-Hodgkin's lymphoma using a Canadian population-based case-control study, the National Enhanced Cancer Surveillance Study. Non-Hodgkin's lymphoma cases (n=638) diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls (n=1,930) were identified from the Ontario Ministry of Finance Property Assessment Database. Antidepressant medication use was ascertained using a self-administered questionnaire. Multivariate logistic regression was used to estimate odds ratios. "Ever" use of antidepressant medications was not associated with non-Hodgkin's lymphoma risk. The odds ratio for non-Hodgkin's lymphoma with 25 or more months of tricyclic antidepressant medication use was 1.6; however, this was nonsignificant. Duration or history of use or individual types of antidepressant medications were not associated with non-Hodgkin's lymphoma risk. These findings do not support an increased risk of non-Hodgkin's lymphoma with antidepressant medication use.
Article
While for most cancers incidence and mortality are decreasing, those of non-Hodgkin's lymphoma (NHL) are steadily increasing. Research to define reasons for this increase is extensive, but has not yet resolved them. We have conducted a literature analysis on trends regarding changes in the incidence, geographic distribution, and etiologic factors of NHL. From our own and previous analyses, an increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence. This rise has been noted worldwide, particularly in elderly persons >55 years. Concerning gender subgroups, a male predominance throughout all age groups is apparent. Although the NHL incidence has historically been higher in whites than blacks, disproportional increases have recently been observed in the latter group. Increases in high-grade NHL and extranodal disease are predominant. Differences in geographic distribution are striking for follicular lymphoma, which is more common in Western countries than elsewhere. Asians have higher rates of aggressive NHL, T-cell lymphomas, and extranodal disease. In the Middle East, high rates of intestinal extranodal disease are observed, whereas in Africa, endemic Burkitt's lymphoma accounts for a substantial proportion. Risks for developing NHL include immunosuppression and a causal link between infectious agents, and lymphomagenesis has also been determined, particularly for human T-cell leukemia/lymphoma virus type 1 (HTLV-1), Epstein-Barr virus (EBV), and Helicobacter pylori infections. Exposure to environmental agents and occupational risks have been studied; however, their significance is as yet uncertain.
Article
Few studies have examined obesity and risk for multiple myeloma, and the results are inconsistent. Laboratory evidence suggests mechanisms through which obesity could influence carcinogenesis of this hematopoietic malignancy. We examined the association between anthropometric characteristics and incident multiple myeloma in a prospective, population-based sample of 37,083 postmenopausal women. In 1986, the women completed a mailed questionnaire that included self-report of height and weight, and friend measurement of waist and hip circumferences. During 16 years of follow up, 95 cases of multiple myeloma were identified through linkage to the Iowa Cancer Registry. In an age-adjusted model, women in the highest category of several anthropometric measurements compared with the lowest category were at increased risk of developing multiple myeloma. For body mass index (kg/m), the rate ratio (95% confidence interval) was 1.5 (0.92-2.6); for weight, 1.9 (1.1-3.4); for waist circumference, 2.0 (1.1-3.5); and for hip circumference, 1.8 (1.0-3.0). Greater adiposity may increase the risk of multiple myeloma.
Article
Obesity has been linked to excess risk for many cancers, but the evidence remains tenuous for some types. Although the prevalence of obesity varies by race, few studies of obesity-related cancer risk have included non-white subjects. In a large cohort of male US veterans (3,668,486 whites; 832,214 blacks) hospitalized with a diagnosis of obesity between 1969 and 1996, we examined risk for all major cancer sites and subsites. Person-years accrued from the date of first obesity diagnosis until the occurrence of a first cancer, death, or the end of the observation period (September 30, 1996). We calculated age- and calendar-year adjusted relative risks (RR) and 95% confidence intervals (CI) for cancer among white and black veterans, comparing obese men to men hospitalized for other reasons, with obesity status as time-dependent. For selected cancers, we performed additional analyses stratified by specific medical conditions related to both obesity and risk of those cancers. To determine whether obesity-related cancer risks differed significantly between white and black men, we evaluated heterogeneity of risk for each cancer site. Among white veterans, risk was significantly elevated for several cancers, including cancers of the lower esophagus, gastric cardia, small intestine, colon, rectum, gallbladder and ampulla of vater, male breast, prostate, bladder, thyroid, and connective tissue, and for malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess risks initially observed for cancers of the liver and pancreas persisted among men without a history of diabetes or alcoholism. Among black veterans, risks were significantly elevated for cancers of the colon, extrahepatic bile ducts, prostate, thyroid, and for malignant melanoma, multiple myeloma, CLL and AML. Obese men are at increased risk for several major cancers as well as a number of uncommon malignancies, a pattern generally similar for white and black men. Due to the increasing prevalence of obesity and overweight worldwide, it is important to clarify the impact of excess body weight on cancer and to elucidate the mechanisms involved.