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Holly EA, Lele C, Bracci PM, McGrath MSCase-control study of non-Hodgkin's lymphoma among women and heterosexual men in the San Francisco Bay Area, California. Am J Epidemiol 150: 375-389
Abstract
A population-based case-control study was conducted between 1988 and 1995 in the San Francisco Bay Area of California to determine risk factors for non-Hodgkin's lymphoma. Participants completed in-person interviews, and blood was drawn to test for viruses and lymphocyte subsets. This report includes data for 1,281 cases and 2,095 controls. In multivariate analyses, the factors associated with a decreased risk for non-Hodgkin's lymphoma were allergy to plants, bee and wasp stings, five or more vaccinations, drugs to lower blood cholesterol, nonsteroidal anti-inflammatory drugs, total number of sexual partners, and lifetime marijuana use, whereas an increased risk was associated with cimetidine and other histamine H2-receptor antagonists, splenectomy, gonorrhea, and body mass index. Unique to sex-specific models was an increased risk for endocrine gland disorders among women and for polio among men. Median CD3, CD4, CD8, CD20, and lymphocyte counts for non-Hodgkin's lymphoma patients were significantly lower than those for controls. These results implicate environmental factors that may influence the early stages of lymphomagenesis by stimulating the immune system. Antigen-driven B cells that accumulate to form lymphoma may be suppressed by immunologic stresses such as exposure to an increased number of sexual partners and to certain medications. A history of allergies provides evidence for a persistent capacity for B-cell differentiation and therefore a decreased accumulation of B cells. The decreased risk for non-Hodgkin's lymphoma with use of nonsteroidal anti-inflammatory drugs and cholesterol-lowering drugs is consistent with a macrophage inflammatory role in B-cell proliferation.
... Although vaccinations are of potential interest in the etiology of lymphoma, only a relatively few studies have assessed vaccinations and lymphoma risk, with mainly null or protective associations reported (7)(8)(9)(10)(11)(12)(13)(14)(15). However most of these studies were small (<1,000 cases; refs. ...
... However most of these studies were small (<1,000 cases; refs. 7,11,12,14,15); had limited data for lymphoma subtypes (11)(12)(13)(14)(15) or used an outdated classification (9,10,13,14); or had limited ability to address potential confounding factors beyond age and sex (10,11,14,15). To address these limitations, we present data from a large case-control study on the association of history of vaccination against yellow fever, hepatitis A, hepatitis B, and influenza with risk of lymphoma. ...
... However most of these studies were small (<1,000 cases; refs. 7,11,12,14,15); had limited data for lymphoma subtypes (11)(12)(13)(14)(15) or used an outdated classification (9,10,13,14); or had limited ability to address potential confounding factors beyond age and sex (10,11,14,15). To address these limitations, we present data from a large case-control study on the association of history of vaccination against yellow fever, hepatitis A, hepatitis B, and influenza with risk of lymphoma. ...
Background:
Vaccinations have been hypothesized to play a role in lymphoma etiology, but there are few studies, mixed results and limited data on lymphoma subtypes. Herein, we investigate the association of vaccinations with risk of major lymphoma subtypes.
Methods:
We studied 2461 lymphoma cases and 2253 controls enrolled from 2002-2014. Participants self-reported history of vaccinations against hepatitis A, hepatitis B, yellow fever and influenza. Polytomous logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals(CI), adjusting for potential confounders.
Results:
After multivariable adjustment, vaccination against influenza was inversely associated with lymphoma (OR=0.82,95%CI:0.66-1.02), which was stronger for last vaccination 1+ years before enrollment (OR=0.71,95%CI:0.56-0.91) and for >5 influenza vaccinations (OR=0.56,95%CI:0.46-0.68). Ever vaccination against hepatitis A (OR=0.81,95%CI:0.66-1.00) but not hepatitis B (OR=0.97,CI:0.81-1.18) was associated with lymphoma risk, although more recent vaccinations were inversely associated with lymphoma risk for both hepatitis A (<6 years before enrollment, OR=0.56,95%CI:0.40-0.77) and hepatitis B (<9 years before enrollment, OR=0.72,95%CI:0.55-0.93). Ever vaccination against yellow fever was inversely associated with risk (OR=0.73,95%CI:0.55-0.96) and this did not vary by time since last vaccination. While there was no overall statistical evidence for heterogeneity of vaccination history by lymphoma subtype, the only statistically significant inverse associations were observed for influenza and yellow fever vaccinations with diffuse large B-cell and follicular lymphoma.
Conclusions:
Selected vaccinations were inversely associated with lymphoma risk, with time since last vaccination relevant for some of these vaccines.
Impact:
Vaccinations against hepatitis A, hepatitis B, yellow fever and influenza are unlikely to increase lymphoma risk.
... Helicobacter pylori is more commonly transmitted between children in large families compared with small families, presumably because of more opportunities for oral transmission (13). Several studies have found a positive association between sibship size, birth order, and NHL (3,4,14,15), although in a large multicenter study, Grulich et al. (16) concluded that selection bias could explain these associations. Sibship size and birth order have been considered surrogates for childhood infection, being easier to ascertain from adult subjects than specific microbial exposures in childhood. ...
... We confirmed the previously reported negative association between atopic disease and NHL (3,4,8,15,(29)(30)(31)(32). The odds ratios in our study were generally stronger in magnitude than those previously reported. ...
... Within twin pairs, a higher frequency of likely childhood exposure to microbial agents was associated with NHL. The finding is consistent with earlier studies showing a positive association between late birth order (a surrogate for childhood crowding and early-life exposure to infection) and increased NHL risk (3,4,14,15), and it is also consistent with the negative association with IM. Both of these associations suggest that more early opportunity for microbial exposure (and thus infection) is associated with a subsequent risk of NHL. ...
We evaluated the association between common immune system-altering experiences and non-Hodgkin lymphoma (NHL) risk using a case-control study of 162 like-sex twin pairs discordant for NHL, identified from the International Twin Study. Information on medical history and evidence of childhood exposure to microbes was obtained by questionnaire from 1998 to 2002. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Intra-twin-pair agreement between twins on individual exposures was high (76%-97%). A negative association between NHL and seasonal hay fever (odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.10, 0.75) and certain allergies (OR = 0.29, 95% CI: 0.13, 0.68) was observed. The number of atopic diseases was negatively associated with NHL (P for trend = 0.0003). A history of infectious mononucleosis was negatively associated with NHL risk (OR = 0.35, 95% CI: 0.14, 0.90). NHL risk was associated with more frequent childhood exposure to microbes during early life (P for trend = 0.04). No differences in association by NHL subtype were observed, although statistical power for these comparisons was low. These observations support the hypothesis that immune-related exposures, especially atopy, are associated with decreased NHL risk. Use of the within-twin-pair study design mitigates confounding by genome, family structure, and unmeasured characteristics of early childhood factors.
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... One study that could have been relevant to our meta-analysis was excluded because it did not present any measure of RR or raw data that could be used. We contacted the authors for further information but were ultimately unable to obtain the data due to the fact that they were no longer available [17]. One study that could have been relevant to our meta-analysis was excluded because it did not present any measure of RR or raw data that could be used. ...
... One study that could have been relevant to our meta-analysis was excluded because it did not present any measure of RR or raw data that could be used. We contacted the authors for further information but were ultimately unable to obtain the data due to the fact that they were no longer available [17]. ...
Hematologic malignancies cause more than half a million deaths every year worldwide. Analgesics were suggested as chemopreventive agents for several cancers but so far, results from individual studies about the relationship between paracetamol (acetaminophen) use and hematologic malignancies are conflicting. Therefore, we decided to perform a systematic review and meta-analysis. We retrieved studies published in any language by systematically searching Medline, Embase, Conference Proceedings Citation Index, Open Access Theses and Dissertations, and the five regional bibliographic databases of the World Health Organization until December 2020. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated according to the inverse of their variances. We performed separate analyses by histologic type. We also evaluated publication bias and assessed quality. A total of 17 study units met our inclusion criteria. The results show an association of hematologic malignancies with any paracetamol intake (OR 1.49, 95% CI 1.23–1.80) and with high paracetamol intake (OR 1.77, 95% CI 1.45–2.16). By subtype, risk was higher for multiple myeloma (OR 2.13, 95% CI 1.54–2.94) for any use and OR 3.16, 95% CI 1.96–5.10 for high intake, while risk was lower and non-significant for non-Hodgkin lymphoma. This meta-analysis provides evidence that paracetamol intake may be associated with hematologic malignancies and suggests that a dose–response effect is plausible. These results are unlikely to be due to publication bias or low quality of studies. Future research should focus on assessing the dose–response relationship.
... Several case-control studies, including one of the largest studies 100 , have found elevated risks of NHL in association with excess weight [113][114][115] However, some studies did not find an association 104,105,112 . Among the cohort studies, some have observed risk increases 99,108 , other studies no association 94,95,98,102,111 and a few studies different results for men and women 97,110 . ...
... Two other studies observed a risk increase for NHL in association with obesity in women, but not in men 97,110 . Some case-control studies have shown increased risks 109,[113][114][115] , including one of the largest studies 100 , while others have not found an association 104,105,112 . In summary, the studies regarding excess body weight and risk of NHL are inconsistent. ...
... Body mass index (BMI), an indirect measure of adiposity, has been linked to the risk of NHL. Results from epidemiologic studies, however, have been inconsistent [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Some studies reported a positive association between BMI and risk of NHL 10,[14][15][16]18,19,[21][22][23] , while others found no association. ...
... Results from epidemiologic studies, however, have been inconsistent [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Some studies reported a positive association between BMI and risk of NHL 10,[14][15][16]18,19,[21][22][23] , while others found no association. [7][8][9]11,12,17,20 . ...
We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in DNA repair pathway genes may modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared to those with BMI < 25, women with BMI ≥ 25 had significantly increased risk of NHL among women who carried BRCA1 (rs799917) CT/TT, ERCC2 (rs13181) AA, XRCC1 (rs1799782) CC, and WRN (rs1801195) GG genotypes, but no increase in NHL risk among women who carried BRCA1 CC, ERCC2 AC/CC, XRCC1 CT/TT, and WRN GT/TT genotypes. A significant interaction with BMI was only observed for WRN (rs1801195, P=0.004) for T-cell lymphoma and ERCC2 (rs13181, P=0.002) for diffuse large B-cell lymphoma. The results suggest that common genetic variation in DNA repair pathway genes may modify the association between BMI and NHL risk.
... Seven case-control studies with available data on cigarette smoking status and NAT1 or NAT2 genotypes were identified through the InterLymph consortium. The seven studies included four from the United States (Nebraska [10], National Cancer Institute-Surveillance Epidemiology End Results (NCI-SEER) [11], Yale University/Connecticut (Yale) [12], and University of California at San Francisco (UCSF2) [13]), two from Europe (Scandinavian Lymphoma Etiology (SCALE) [14], and EpiLymph [15]), and one from Australia (New South Wales [16]). Genotype data for NAT1 were available for four studies (New South Wales, Nebraska, NCI-SEER, Yale), whereas NAT2 data were available for six studies (all but New South Wales). ...
... Genotype data for NAT1 were available for four studies (New South Wales, Nebraska, NCI-SEER, Yale), whereas NAT2 data were available for six studies (all but New South Wales). Methodological details of the individual studies have been published previously [10][11][12][13][14][15][16] and are summarized in Table 1. Analyses were restricted to non-Hispanic white participants. ...
Purpose:
Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2.
Methods:
We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models.
Results:
Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes.
Conclusion:
The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.
... Similarly, different studies have found that a 5 kg/m 2 increase from normal BMI in men and women was also associated with the increased risk of NHL [45][46][47]59]. Of note, some factors, such as age, ethnicity, smoking status, alcohol consumption, gender [50,[60][61][62], and probably menopause [44], should be considered since they have been found to increase the overall risk of the disease in obese people. Regarding responses to treatments, salvage chemotherapy and high-dose chemotherapy following autologous hematopoietic stem cell transplantation have been successfully tested as promising treatments in patients with relapsed lymphoma [63,64]. ...
Obesity, which is considered a pandemic due to its high prevalence, is a risk factor for many types of cancers, including lymphoma, through a variety of mechanisms by promoting an inflammatory state. Specifically, over the last few decades, obesity has been suggested not only to increase the risk of lymphoma but also to be associated with poor clinical outcomes and worse responses to different treatments for those diseases. Within the extensive range of proinflammatory mediators that adipose tissue releases, leptin has been demonstrated to be a key adipokine due to its pleotropic effects in many physiological systems and diseases. In this sense, different studies have analyzed leptin levels and leptin/leptin receptor expressions as a probable bridge between obesity and lymphomas. Since both obesity and lymphomas are prevalent pathophysiological conditions worldwide and their incidences have increased over the last few years, here we review the possible role of leptin as a promising proinflammatory mediator promoting lymphomas.
... There was no association for anal, penile, or non-Hodgkin's lymphoma (52)(53)(54). Two other studies on non-Hodgkin's lymphoma and bladder cancer reported decreased cancer risks (55)(56)(57). ...
Cannabis has certain health benefits, but some people may experience harms from use. Co-use of tobacco and cannabis is common. Smoke from cannabis contains many of the same carcinogens and toxicants as the smoke from tobacco, raising concerns that cannabis smoking may be a risk factor for cancer. With growing access to and acceptance of medical and nonmedical cannabis, there is an urgent need to understand the risks and benefits of the current modes of cannabis use and how cannabis may be associated with cancer risk. This monograph summarizes a session from a National Cancer Institute Symposium on nonmedical cannabis use and cancer risk. We had 3 objectives: describe the relation between nonmedical cannabis use and cancer risk, delineate patterns and correlates of cannabis co-use with tobacco, and document potentially harmful inhalational exposure resulting from smoked and vaped cannabis. Methodological limitations in the literature and future research recommendations are provided.
... As for the mere epidemiological aspect, two reports on non-Hodgkin's lymphoma, which included 378 subjects [172] and 1,281 cases and 2,095 controls [173] demonstrated null to inverse correlations with marijuana use. However, parental marijuana intake in pregnant women has been correlated with childhood tumor development, including leukemia [174]. ...
The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.
... However, no increase of stomach, esophageal, colon or rectal cancer was observed in ranitidine-treated patients (Fioretti et al. 1997;La Vecchia 2002). An excess risk of non-Hodgkin's lymphoma was reported to be associated with use of H2 receptor antagonists (including ranitidine users which, however, were not separately analyzed) which was suggested by the authors to have been due to longterm infection with Helicobacter pylori and not with the use of any individual gastric acid lowering drug such as ranitidine (Holly et al. 1999). Taken together, ranitidine may rightfully be regarded as not carcinogenic up to the highest recommended doses of use and with a large margin of safety above that. ...
Several N-vinyl compounds are produced in high volumes and are widely employed in the production of copolymers and polymers used in chemical, pharmaceutical, cosmetic and food industry. Hence, information on their genotoxicity and carcinogenicity is requisite. This review presents hitherto available information on the carcinogenicity and genotoxicity of N-vinyl compounds as well as their metabolism potentially generating genotoxic and carcinogenic derivatives. The genotoxicity and carcinogenicity of the investigated N-vinyl compounds vary widely from no observed carcinogenicity tested in lifetime bioassays in two rodent species (up to very high doses) to carcinogenicity in rats at very low doses in the absence of apparent genotoxicity. Despite of the presence of the vinyl group potentially metabolized to an epoxide followed by covalent binding to DNA, genotoxicity was observed for only one of the considered N-vinyl compounds, N-vinyl carbazole. Carcinogenicity was investigated only for two, of which one, N-vinyl pyrrolidone was carcinogenic (but not genotoxic) and ranitidine was neither carcinogenic nor genotoxic. As far as investigated, neither a metabolically formed epoxide nor a therefrom derived diol has been reported for any of the considered N-vinyl compounds. It is concluded that the information collected in this review will further the understanding of the carcinogenic potentials of N-vinyl compounds and may eventually allow approaching their prediction and prevention. A suggestion how to prevent genotoxicity in designing of N-vinyl compounds is presented. However, the available information is scarce and further research especially on the metabolism of N-vinyl compounds is highly desirable.
... In the context of this study, high risk of selection bias was defined as failure to adequately adjust for tobacco use. Elimination of studies with high risk of selection bias thus involved eliminating studies that failed to adjust for tobacco use, or those that compared user and nonuser populations that universally or predominantly use tobacco, 62,64,72,73,81,87 due to the inability to adequately adjust for tobacco use in this scenario. ...
Introduction: Cannabis smoke contains carcinogens similar to tobacco, in addition to compounds with antitumor activity. Cannabis use reduces the risk of obesity and cannabinoids inhibit chronic inflammation, known causes of cancer. The net effect of Cannabis use on cancer risk is not known.
Objective: To examine the association between Cannabis use and cancer risk in the United States.
Methods: Identify and analyze published data on cancer risk in Cannabis users.
Results: A total of 55 data points, consisting of risk ratios of cancer in Cannabis users and nonusers, were identified from 34 studies. Of these, 5 did not contain data essential for inclusion in the meta-analysis. The remaining data showed a nonsignificant trend to an association with reduced risk (relative risk [RR]=0.90, p>0.06, N=50) although heterogeneity is high (I²=72.4%). Removal of data with high risk of selection bias (defined as those from North Africa and those that failed to adjust for tobacco) and data with high risk of performance bias (defined as those with fewer than 20 cases or controls among Cannabis users) resulted in an RR <1.0 (RR=0.86, p<0.017, N=24) and large effect size (Hedges g=0.66), but did not decrease heterogeneity (I²=74.9). Of all cancer sites, only testicular cancer showed an RR value >1, although this was not significant and had a negligible effect size (RR=1.12, p=0.3, Hedges g=0.02). Following removal of testicular cancers the remaining data showed a decrease in risk (RR=0.87, p<0.025, N=41). Cancers of the head and neck showed a negative association with cancer risk (RR=0.83, p<0.05), with a large effect size (Hedges g=0.55), but high heterogeneity (I²=79.2%). RR did not reach statistical significance in the remaining cancer site categories (lung, testicular, obesity-associated, other). The data are consistent with a negative association between Cannabis use and nontesticular cancer, but there is low confidence in this result due to high heterogeneity and a paucity of data for many cancer types.
... Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. A summary of study details is provided in Supplemental Table 1 with additional details available in previous InterLymph publications [4,5,10,25,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. ...
PurposeWe explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case–control analysis.MethodsA total of 7,926 NHL patients and 10,018 controls from 12 case–control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17–96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. PACT was used to account for multiple comparisons.ResultsThere was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (pinteraction = 0.04, ORinteraction = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (pinteraction = 0.03, ORinteraction = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.Conclusions
Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.
... Four studies 26,[47][48][49] addressed marijuana use and the development of other cancers; all were performed in the United States (eTable 4 in the Supplement). A large, prospective study 48 found an association between the development of malignant primary adult-onset glioma and weekly (n = 6002; RR, 3.2; 95% CI, 1.1-9.2) and monthly (n = 4699; RR, 3.6; 95% CI, 1.3-10.2) marijuana smoking compared with nonuse. ...
Importance
Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear.
Objective
To assess the association of marijuana use with cancer development.
Data Sources
A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.
Study Selection
English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm.
Data Extraction and Synthesis
Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus.
Main Outcomes and Measures
Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs.
Results
Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I² = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I² = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.
Conclusions and Relevance
Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana’s association with lung, oral, and other cancers.
Trial Registration
PROSPERO identifier: CRD42018102457
... 25,27 There are conflicting data about assoc iations with head and neck squamous cell carcinoma, 25,27,28 bladder cancer, 25,29 and non-Hodgkin's lymphoma. 25,30 Some studies suggest marijuana offers protection against certain types of cancer. In fact, it appears that some cannabinoids found in marijuana, such as cannabidiol (CBD), may be antineoplastic. ...
Marijuana use can cause concerning physical, psychomotor, cognitive, and psychiatric effects, not to mention a near-doubling of car accidents.
... there was no further increase with increases in number of pills per day or number of years used. The study of Holly et al. [63] provided no data, but in their manuscript the authors stated that there was no association of non-Hodgkin's lymphoma with use of AC. ...
Acetaminophen has several pharmacologic properties that suggest it could be carcinogenic in human beings. A number of epidemiologic studies have been conducted to examine whether use of acetaminophen actually predisposes to the occurrence of one or more forms of cancer. There are inherent limitations to many of these studies, including the inaccurate identification of users and nonusers of acetaminophen, relatively short follow-up for cancer incidence, and the potential for confounding by indication. The present manuscript reviews the results of epidemiologic studies of acetaminophen use in relation to cancer incidence published through the end of 2015. The limitations of the underlying studies notwithstanding, some interim conclusions can be reached. For all but several forms of cancer, there is no suggestion that persons who have taken acetaminophen are at altered risk, even persons who have consumed a large quantity of the drug or those who have taken it for an extended duration. While in some studies the incidence of renal cell carcinoma has been observed to be increased among acetaminophen users, several other studies have failed to observe any such association; the reason for the discrepant findings is unclear. Some of the small number of studies that have presented data on the incidence of lymphoma, leukemia, and plasma cell disorders have found the risk to be modestly higher in users than nonusers of acetaminophen, but the results of other studies of these malignancies will be needed to gauge the possible role of publication bias as the basis for the positive results.
... Alternatively, the mechanism may be similar to that underlying the inverse association between atopy and helminth infections (both Th2-driven) and/or between atopy and measles and tuberculosis (diseases that mediate immunosuppression via cytokines dominant in pancreatic cancer patients (30,37)). An inverse association with history of allergies has also been observed in epidemiologic studies for other gastrointestinal cancers, including colorectal (38,39) and liver (40) cancers, non-Hodgkin's lymphoma (41)(42)(43), and glioma (19,44). Detailed data from previous studies that examined the association between allergies and pancreatic cancer are limited. ...
Data from a large population-based case-control study conducted in the San Francisco Bay Area between 1994 and 2001 were analyzed to examine the association between pancreatic cancer and history of allergic conditions. Pancreatic cancer cases (n = 532) had to be 21–85 years of age and were identified using rapid case ascertainment. Random digit dialing and Health Care Financing Administration lists (age, ≥65 years) were used to obtain 1,701 controls who were frequency-matched to cases by sex and age within 5 years. In-person interviews were conducted and detailed allergy history data were obtained for all participants. Prior history of any allergy was associated with a reduced risk estimate for pancreatic cancer (odds ratio (OR) = 0.77, 95% confidence interval (CI): 0.63, 0.95). Inverse associations were observed for common allergens, including house dust (OR = 0.72, 95% CI: 0.54, 0.94), cats (OR = 0.59, 95% CI: 0.41, 0.85), plants (OR = 0.77, 95% CI: 0.62, 0.96), and mold (OR = 0.49, 95% CI: 0.32, 0.75), and for all allergic symptoms, although some confidence intervals included unity. Trends were observed for decreased risks associated with increasing number of allergies (p = 0.0006) and severity of allergic symptoms (p = 0.003). These results provide support for the plausibility that immune function in relation to allergies may play a role in the etiology of pancreatic cancer. allergy and immunology; pancreatic neoplasms
... Data were provided via the InterLymph Data Coordinating Center (DCC) at the Mayo Clinic, Rochester, which was established in 2009 to centrally standardise and harmonise study data so that consistent datasets could be produced to expedite pooling projects. Descriptions of the included studies have been published (12)(13)(14)(15)(16)(17)(18)(19)(20); a brief outline is given in Table 1. Cases were ascertained using rapid identification techniques, and controls were randomly selected from population registers (6 studies), outpatient clinics (1 study) or hospital inpatients with non-neoplastic conditions (2 studies). ...
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.
... Some studies have shown: there is no relationship between cigarette smoking and Non-Hodgkin Lymphoma [11][12][13][14][15]. In the third occupational group (working with metals) NHL was significantly higher in patients rather than control group [OR= 4.6 (1.47-14.35) ...
Background
Lymphoma is a malignancy, arises from lymphoid tissue. Nowadays, it is the ninth most common cancer in Iran. The risk factors of malignant lymphomas have not well determined, but since 20 years ago till now, too many epidemiological researches have been concerning either Non-Hodgkin Lymphoma (NHL) or Hodgkin's Disease (HD). It is a common usual hypothesis that idiosyncratic reaction to common physical, chemical, and viral agents could lead to lymphoma without obvious immune deficiency. Some occupations has reported to cause increasing "NHL" risks, such as rubber industry, veterinaries, uranium mining, metal working, asbestos exposing, farming, textile industry, and benzene exposing. The roles of ionizing radiation, benzene and other environmental agents have not been clear, because of the lack of confirmed evidences for relation between the occupational and environmental agents with "HD".
Methods
A case-control study with 150 cases of malignant lymphoma and 150 controls have performed in Tehran. Data have selected through face-to-face interviews about the medical and occupational histories.
Results
In this study, there was a significantly increased risk for Non-Hodgkin Lymphoma in these occupations; welders, metal workers, founders, aluminium workers OR=4.6 [Confidence Interval (CI): 1.47-14.35] and increased risk for Hodgkin's Disease in drivers OR=2.34 [(CI):0.86-6.35]. We have found out decreased NHL risk in office workers OR=0.54 [(CI):0.29-1.02] and also found out a non-significant increased NHL risk in farmers OR=1.58 [(CI):0.82-3.03]. In this study, we have found no relation between smoking and HD, or NHL.
Conclusion
The results of this study suggest that several occupations could alter the risk of Non-Hodgkin Lymphoma and Hodgkin's Disease.
... Interestingly, however, evidence suggests that several allergic conditions are associated with a reduced risk of NHL. A decrease in risk has repeatedly been observed in individuals with allergic skin conditions or with a history of allergy to grass or pollen (93,(198)(199)(200)(201)(202). However, the majority of these studies have used self-reported history of allergy, and the distinction between non-allergic conditions and allergy has not always been clear. ...
... A less plausible explanation could point to the antitumor activity of histamine [81], a chemical mediator of allergic reactions that protects natural killer cells and T cells against oxygen radicalinduced damage and death by suppressing oxygen radical formation, and also optimizes lymphocyte activation by cytokines [82]. Clinical trials in malignancies such as metastatic malignant melanoma and acute myeloid leukemia have demonstrated that histamine dihydrochloride in combination with immunotherapy has the potential to improve treatment outcome, further supporting the posssible antitumour effect of histamine [83,84]. ...
Increasing evidence indicates that a dysregulated immune system, as the one found in allergic disorders, can affect survival of tumor cells. A possible association between allergies and risk of hematologic malignancies has been examined in several epidemiological studies, however, results were not always consistent.
The aim of this review is to report the preclinical and clinical data, which support a correlation between allergy and hematologic neoplasms.
Immune system modulation could represent a powerful tool in the prevention and treatment of hematologic malignancies.
... For example, the case-control study cited by Harris that reported an inverse association of NSAIDs with risk of NHL was based only on an analysis of ever vs. never use of any NSAIDs for 4 or more consecutive weeks. 2 The 2nd concern was the lack of a dose response, which was deemed "not consistent with causality." We believe that it is premature to evaluate whether this a causal association, but it is accepted that a lack of dose response does not preclude a causal association. 3 Third, and most seriously, is the concern that the association of NSAIDs with NHL risk is potentially confounded "with inflammation, treatment and immunosuppression in not just rheumatoid arthritis (RA) but a myriad of other immunosuppressive disorders and medications that have been etiologically linked to NHL development." ...
... The effect of allergies on FL risk has been debated. Some studies have found significant associations [45][46][47][48][49][50][51] but others have not [52][53][54][55][56][57][58][59]. In 2001, Briggs et al. found no evidence that a general history of allergy was associated with NHL overall (OR = 1.0, 95% CI 0.8-1.2) or for its major subtypes [60]. ...
Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair gene XRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment.
We aimed to systematically evaluate the association between allergic conditions and the risk of Hodgkin’s lymphoma (HL) and non-HL (NHL). Systematic literature searches in PubMed and Embase were conducted up to October 2015 to identify eligible studies. Either a fixed-effects model or a random-effects model was adopted to estimate overall odds ratios (ORs) according to heterogeneity across studies. Subgroup and publication bias analyses were applied. A total of 24 case–control studies and 13 cohort studies (conducted from 1987 to 2015) were included in the analysis of the risk of NHL. History of any allergic condition was inversely associated with the risk of NHL in case–control studies (OR =0.83, 95% CI 0.76–0.91), while the reduction in the risk of NHL was not observed in cohort studies (OR =1.18, 95% CI 0.98–1.42). Significant association with the risk of NHL was found for asthma, hay fever, food allergy, allergic rhinitis, and hives. In the pooled analysis of the risk of HL, 12 studies (two were cohort studies) were included. The pooled OR was 0.96 (95% CI 0.84–1.09) for case–control studies and 1.46 (95% CI 0.63–3.38) for cohort studies. For specific allergic condition, we observed a reduced risk of HL in individuals with hay fever and food allergy. In conclusion, history of any allergic condition was not significantly associated with the risk of NHL or HL. Several specific allergic conditions, including asthma, hay fever, food allergy, and allergic rhinitis, might be associated with a reduced risk of NHL, while individuals with hay fever or food allergy may have a reduced risk of HL.
Individuals infected with HIV are at increased risk of developing aggressive non-Hodgkin's lymphoma with a worse prognosis than those similarly afflicted without HIV infection. The underlying genetic differences in tumor behavior between these two groups are not known. We explored the hypothesis that lymphomas from HIV-positive individuals have distinct somatic genetic changes that may provide clues to the genetic basis of disease progression and outcome. Genome-wide DNA copy number alterations (CNAs) in primary tumors from 14 HIV-positive and 11 HIV-negative patients with diffuse large B-cell lymphoma (DLCL) were quantified using comparative genomic hybridization (CGH). Tumors from HIV-positive patients displayed fewer regional DNA-CNAs than those from patients who did not have HIV. When CNAs were present, they occurred at lower frequency in HIV-positive patients. Gains at chromosomes 8q and Xp were the most frequent changes in the HIV-negative group, and gains on 2p and 12q were common in the combined HIV-positive and HIV-negative groups. No alteration was specific to AIDS-related DLCL. These data suggest that fewer somatic genomic changes are needed for progression to DLCL in HIV-immunocompromised hosts, and that other factors, such as reduced immune surveillance, may contribute to neoplastic progression.
(C) 2001 Lippincott Williams & Wilkins, Inc.
Thèse portant sur l'étude de trois plantes psychotropes consommées en Nouvelle-Calédonie : kava, cannabis et datura. L'étude porte plus spécifiquement sur les aspects médicaux et médico-légaux.
Mounting evidence appears to link asthma and atopy to cancer susceptibility. This review presents and discusses published epidemiological studies on the association between site-specific cancers and atopy. PubMed was searched electronically for publications between 1995 and 2015, and cited references were researched manually. Quantitative studies relating to atopy, allergy, or asthma and cancer were identified and tabulated. Despite many exposure-related limitations, patterns in the studies were observed. Asthma, specifically, has been observed to be a risk factor for lung cancer. A protective effect of atopic diseases against pancreatic cancer has been shown consistently in case-control studies but not in cohort studies. Allergy of any type appears to be protective against glioma and adult acute lymphoblastic leukemia. Most studies on atopic diseases and non-Hodgkin lymphoma or colorectal cancer reported an inverse association. The other sites identified had varying and non-significant outcomes. Further research should be dedicated to carefully defined exposure assessments of “atopy” as well as the biological plausibility in the association between atopic diseases and cancer.
Non-Hodgkin lymphomas (NHL) are expected to account for 4.2% of cancer diagnoses and 3.3% of cancer deaths in the United States in 2006. With approximately 58,870 cases diagnosed and 18,840 deaths from NHL expected in 2006, this group of malignancies constitutes a serious public health problem in the United States as it does in most developed countries. This chapter reviews the epidemiology of NHL. Topics covered include classification, molecular characteristics, demographic patterns, and host factors.
This chapter discusses the immunologic factors in cancer. Topics covered include structure and function of the immune system, immune variation and cancer risk, and agerelated changes in immune function. Experience with a wide range of immune deficient conditions indicates that loss of immune competence does not globally increase cancer incidence. Limited sets of malignancies are increased that are specific to the underlying immune abnormalities. A common feature is the prominent excess of non-Hodgkin lymphoma (NHL) in many of these disorders.
The third edition of this book reviews the global burden of cancer, causes of cancer, and current priorities and future directions in cancer epidemiology and prevention research. The book maintains the structure of previous editions with seventy-two chapters organized into five major sections: Basic Concepts; The Magnitude of Cancer; The Causes of Cancer; Cancer by Tissue of Origin, and Cancer Prevention and Control. The introductory chapters under Basic Concepts highlight the advances in genomic and molecular biology that have applications in morphologic classification of malignant tumors, and in the elucidation of critical genetic events that result in malignant transformation and tumor invasion. The section on the Magnitude of Cancer reviews global patterns of cancer incidence and mortality in relation to country of residence, age, gender, race and ethnicity, and socioeconomic status. The section on The Causes of Cancer reviews the spectrum of environmental, lifestyle and genetic risk factors that are associated with the origin of human cancers. Chapters on Cancer by Tissue of Origin review systematically the demographic, environmental, and host factors that impact the origin and progression of cell-and organ-specific neoplasms. The concluding section, Cancer Prevention and Control, addresses methods and applications for translating epidemiologic, laboratory, and clinical research observations into preventive interventions. Special emphasis is provided on measuring the impact of behavioral interventions on health-promoting practices, as well as governmental policies that regulate environmental carcinogens.
Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that aberrant induction of COX-2 and up-regulation of the prostaglandin cascade play a significant role in carcinogenesis, and reciprocally, blockade of the process has strong potential for cancer prevention and therapy. Supporting evidence includes the following: [1] expression of constitutive COX-2-catalyzed prostaglandin biosynthesis is induced by most cancer-causing agents including tobacco smoke and its components (polycylic aromatic amines, heterocyclic amines, nitrosamines), essential polyunsaturated fatty acids (unconjugated linoleic acid), mitogens, growth factors, proinflammatory cytokines, microbial agents, tumor promoters, and other epigenetic factors, [2] COX-2 expression is a characteristic feature of all premalignant neoplasms, [3] COX-2 expression is a characteristic feature of all malignant neoplasms, and expression intensifies with stage at detection and cancer progression and metastasis, [4] all essential features of carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis, and immunosuppression) are linked to COX-2-driven prostaglandin (PGE-2) biosynthesis, [5] animal studies show that COX-2 up-regulation (in the absence of genetic mutations) is sufficient to stimulate the transformation of normal cells to invasive cancer and metastatic disease, [6] non-selective COX-2 inhibitors, such as aspirin and ibuprofen, reduce the risk of human cancer and precancerous lesions, and [7] selective COX-2 inhibitors, such as celecoxib, reduce the risk of human cancer and precancerous lesions at all anatomic sites thus far investigated. Results confirming that COX-2 blockade is effective for both cancer prevention and therapy have been tempered by observations that some COX2 inhibitors pose a risk to the cardiovascular system, and more studies are needed in order to determine if certain of these drugs can be taken at dosages that prevent cancer without increasing cardiovascular risk. It is emphasized that the "inflammogenesis model of cancer" is not mutually exclusive and may in fact be synergistic with the accumulation of somatic mutations in tumor suppressor genes and oncogenes or epigenetic factors in the development of cancer.
Leptin is an adipose-derived cytokine that have important role in bodyweight homeostasis and energy balance. There are a number of studies which have suggested that leptin and its receptors dysregulation play critical role in the development of malignancies including hematological malignancies, mainly via activation of JAK/STAT pathway which regulates downstream signaling pathways such as PI3K/AKT signaling and ERK1/2. In this review, current understandings of leptin/leptin receptors mediated pathogenesis in various lymphoid malignancies are described. Blocking of the leptin receptor might be a unique therapeutic approach for many hematological malignancies.
Over the past few decades, the rate of cancer diagnosis has increased worldwide due to the increase in population and average life
expectancy, and also, due to the advances in diagnostic medical technology that facilitate early cancer detection and recognition.
Nonetheless, the treatment options have not been developed proportional to this increase, with a huge number of patients frequently
being diagnosed with different types of fatal cancer. This has prompted different health organizations to search for novel strategies to
prevent cancer, or even halt its progression. Having failed to provide optimum vascular protection benefits, especially with the introduction
of relatively superior antiplatelets, such as adenosine diphosphate (ADP) receptor inhibitors; clopidogrel and ticagrelor, regular aspirin use
was proposed to reduce the risk of common cancers like colorectal cancer, gastric cancer, breast cancer, lung cancer, prostate cancer
and haematological malignancies, as suggested by epidemiological studies. However, it is difficult to draw any firm conclusions on such
weak data, as this could raise false hopes among patients and physicians and could potentially mislead scientific research. Clearly,
current evidence highlights a gap in medical research and emphasizes the need to carry out interventional studies in high risk for cancer
patients using specific aspirin doses in order to validate the data. This should also shed some light on the risk-benefit profile in view of
the potential for bleeding complications, especially with the higher doses.
Non-Hodgkin lymphoma (NHL) consists of many histologically and biologically distinct lymphoid malignancies with poorly understood, but possibly distinct, etiologies. The patterns of incidence and time trend vary not only by age, sex, and race/ethnicity in the USA, but also show significant geographic differences, suggesting the potential role of infectious agents, environmental factors, and lifestyle factors in addition to host genetic status in the development of NHL. Important pathogenetic mechanisms include immune modulation and chronic antigen stimulation. Epidemiologic studies in the past two decades have provided intriguing new insights on the possible causes of lymphoma and support the idea that there is some mechanistic commonality of lymphomagenesis, but significant etiologic heterogeneity clearly exists. This review presents a summary of the current understanding of the descriptive epidemiology and etiology of NHL and suggests areas of focus for future epidemiologic research.
A multi-centre, population-based case–control study of lymphoma among adults was conducted in Germany from 1999–2003. The study comprised 700 incident cases (Hodgkin lymphomas and non Hodgkin’s lymphoma, NHL) in the age range 18–80 years and 700 age-, sex- and area-matched controls obtained from population registries. Diagnosis was based on the REAL/WHO classification. Information on demographic characteristics, lifestyle, medical history and occupation was obtained by in-person interviews. Each participant was asked for a 24 ml blood sample.First results are focused on basic demographic characteristics, contact to animals, childhood diseases and vaccinations. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The ORs for lymphoma were decreased for exposure to sheep and goats (OR=0.7; 95% CI=0.5–0.9), for rabbits and hare (OR=0.7; 95% CI=0.5–0.9), measles infection (OR=0.6; 95% CI=0.5–0.9), Bordetella pertussis infection (OR=0.7; 95% CI=0.6–0.95), and tetanus vaccination (OR=0.5; 95% CI=0.3–0.9). Increased risk of lymphoma was associated with exposure to cattle (OR=1.3; 95% CI=1.03–1.7) and immunization for tuberculosis (OR=1.5; 95% CI=0.997–2.4). The results of this study are partly consistent with the hygiene hypothesis. The inconsistencies of some of the findings with an explanation by the Th1/Th2 paradigm, however, warrant further research and may indicate that broader explanatory concepts are needed.
Marijuana use is legal in two states and additional states are considering legalization. Approximately 18 million Americans are current marijuana users. There is currently no consensus on whether marijuana use is associated with cancer risk. Our objective is to review the epidemiologic studies on this possible association. We identified 34 epidemiologic studies on upper aerodigestive tract cancers (n = 11), lung cancer (n = 6), testicular cancer (n = 3), childhood cancers (n = 6), all cancers (n = 1), anal cancer (n = 1), penile cancer (n = 1), non-Hodgkin lymphoma (n = 2), malignant primary gliomas (n = 1), bladder cancer (n = 1), and Kaposi sarcoma (n = 1). Studies on head and neck cancer reported increased and decreased risks, possibly because there is no association, or because risks differ by human papillomavirus status or geographic differences. The lung cancer studies largely appear not to support an association with marijuana use, possibly because of the smaller amounts of marijuana regularly smoked compared with tobacco. Three testicular cancer case-control studies reported increased risks with marijuana use [summary ORs, 1.56; 95% confidence interval (CI), 1.09-2.23 for higher frequency and 1.50 (95% CI, 1.08-2.09) for ≥10 years]. For other cancer sites, there is still insufficient data to make any conclusions. Considering that marijuana use may change due to legalization, well-designed studies on marijuana use and cancer are warranted. Cancer Epidemiol Biomarkers Prev; 24(1); 15-31. ©2015 AACR.
©2015 American Association for Cancer Research.
Background Non-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is
incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers
of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium
therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes.
This article describes in detail the project rationale and design.
CANINE atopic dermatitis (AD) has been defined as ‘a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed to environmental allergens’ (Halliwell 2006). Due to numerous similarities, several studies have demonstrated the usefulness of the canine animal model for human AD (Marsella and Girolomoni 2009, Olivry 2012).
In people, conflicting results have been published on the association between AD and the development of neoplasia; some studies suggest a protective effect of AD against the development of neoplasia due to a possible enhancement of the immune surveillance. Contrary, other studies have hypothesised that a chronic immune stimulation is at the base of the development of neoplastic diseases in people (Vena and others 1985, Hagstromer and others 2005, Wang and Diepgen 2005).
Recently, canine lymphomas have been established as a model for non-Hodgkin's lymphomas (NHLs) in people due to the striking similarities in clinical presentation, genomic instability, and cytological and histological features (Vail and others 2009, Marconato and others 2013). The most common NHL in dogs is multicentric B cell lymphoma (ML) (Teske 1994). Although a high incidence of AD and ML is present in dogs, no studies have been published on the possible association between these two disorders. Therefore, based on the similarities between canine and human AD and NHL, the goal of this study is to explore the association between canine AD and ML.
Medical records of dogs diagnosed with ML, characterised by rapid, non-painful development of generalised peripheral lymphadenopathy with evidence of malignant lymphocytes by histological examination were selected for this case-control study. Systemic clinical signs (eg profound lethargy, weakness, fever, anorexia and dehydration) were also recorded. The main exposure of interest was canine AD, diagnoses based on compatible history, clinical signs and …
Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I2) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90–1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54–0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89–1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01–1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. © 2014 The Authors. Hematological Oncology Published by John Wiley & Sons, Ltd.
Background:
Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM), a rare non-Hodgkin lymphoma subtype, shows strong familial aggregation and a positive association with chronic immune stimulation, but evidence regarding other risk factors is very limited.
Methods:
The International Lymphoma Epidemiology Consortium (InterLymph) pooled data from 11 predominantly population-based case-control studies from North America, Europe, and Australia to examine medical history, lifestyle, family history, and occupational risk factors for LPL/WM. Age-, sex-, race/ethnicity-, and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for a total of 374 LPL/WM cases and 23 096 controls.
Results:
In multivariate analysis including all putative risk factors, LPL/WM risk was associated with history of Sjögren's syndrome (OR = 14.0, 95% CI = 3.60 to 54.6), systemic lupus erythematosus (OR = 8.23, 95% CI = 2.69 to 25.2), hay fever (OR = 0.73, 95% CI = 0.54 to 0.99), positive hepatitis C serology (OR = 2.51, 95% CI = 1.03 to 6.17), hematologic malignancy in a first-degree relative (OR = 1.64, 95% CI = 1.02 to 2.64), adult weight (OR = 0.61, 95% CI = 0.44 to 0.85 for highest vs. lowest quartile), duration of cigarette smoking (OR = 1.46, 95% CI = 1.04 to 2.05 for ≥ 40 years vs. nonsmokers), and occupation as a medical doctor (OR = 5.54, 95% CI = 2.19 to 14.0). There was no association with other medical conditions, lifestyle factors, or occupations.
Conclusions:
This pooled analysis confirmed associations with immune conditions and family history of hematologic malignancy, and identified new associations with hay fever, weight, smoking, and occupation, and no association with other lifestyle factors. These findings offer clues to LPL/WM biology and prevention.
With the advent of legalization of marijuana for medicinal and recreational purposes, and the increase use of marijuana, healthcare providers will be increasingly confronted with marijuana users as patients in clinical environments. While there is vast literature regarding the societal and mental health harms associated with marijuana use, there is a paucity of reviews of the potential consequences of marijuana use on physical health or medical conditions. We examine the recent literature on the physical harms associated with illicit and legal marijuana administration. We surveyed the peer-reviewed medical literature from 1998 to 2013 of studies assessing the association of marijuana use and physical diseases. We conclude that healthcare providers should be cognizant that the existing literature suggests that marijuana use can cause physical harm. However, evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions.
Aim In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures.
Methods All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0–10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure.
Results 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.4) and mineral oils (OR 1.7). Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2).
Conclusions We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.
To divulge the risk factors for non-Hodgkin lymphomas (NHL) in children and adults among pediatricians.
Methods
We performed a literature review of articles published in the last 25 years through the Medline, IAR Cancer and Cancerlit databases. The search profile was “NHL risk factors”. The most interesting papers, as well as the most relevant articles cited and published more than 25 years prior to the search, were selected.
Results
The following risk factors for the development of NHL were reported with greater or lesser evidence: socioeconomic status, family factors, immunodeficiencies, bacterial and viral infections, vaccinations and drugs, radiation, occupational exposure, exposure to animals, diet, and lifestyle.
Conclusions
The etiology of most NHLs is unknown. The most important risk factors are: a) congenital and acquired immunodeficiency; b) viral (human T-cell leukemia virus type-I, Epstein-Barr virus, AIDS virus), and bacterial (Helicobacter pylori) infections; c) therapy with diphenylhydantoin and antineoplastic drugs, and d) exposure to pesticides and organic solvents.
Objectives:
Allergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.
Methods:
The Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998-2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases and 2296 controls with complete occupational history could be included in the analysis. Associations between HMW exposures and lymphoma were evaluated using pooled unconditional logistic regression analyses.
Results:
Individuals exposed to HMW agents had a non-statistically significant decreased risk of any lymphoma (OR, 0.88: 95% CI, 0.74-1.05) and of B-cell lymphoma (OR, 0.91; 95% CI, 0.76-1.09), and a significantly decreased risk for Hodgkin lymphoma (OR, 0.62; 95% CI, 0.40-0.98). A decrease in risk for lymphoma was found for exposure to latex (OR, 0.74; 95% CI, 0.55-0.99).
Conclusions:
Further epidemiologic and mechanistic research is needed to confirm that occupational exposure to HMW agents predisposing to asthma can reduce the risk of lymphoma.
Background:
Several reports point to inverse associations between allergies and ALL; yet, no study has explored this link using both self-reported-data on allergic history and biomarkers of atopic sensitization.
Methods:
Clinical information for the variables of interest was available for 252 out of 292 cases of childhood (0-14 years) ALL, newly diagnosed across Greece over a 4.5 year period as well as for 294 hospital controls. Allergen-specific-IgEs, as markers of allergic predisposition, against 24 most prevalent respiratory and food allergens, were determined, using an enzyme immunoassay procedure for 199 children with ALL and 113 controls. Cases were compared with controls through frequency distributions and unconditional multiple logistic regression models to estimate odds ratios (ORs) and 95% confidence-intervals (CIs) regarding associations of allergy with childhood ALL.
Results:
Self-reported-allergic history overall (OR: 0.49, 95% CI: 0.34-0.72) and practically each one of its main components (respiratory, food, any other clinical allergy) were strongly and inversely associated with ALL. Likewise, the serum IgE inverse association was of the same magnitude (OR: 0.43, 95% CI: 0.22-0.84) mainly contributed by food IgE (OR: 0.39, 95% CI: 0.18-0.83).
Conclusion:
Beyond the already established inverse association of allergic history with childhood ALL, a same magnitude association is evident when serologic markers of allergic predisposition are used as an alternative measure of allergy. Further research with more appropriate study designs is needed to better understand possible associations between prior allergy and childhood ALL risk.
The incidence rates of non-Hodgkin lymphoma (NHL) have steadily increased over the last several decades in the United States, and the temporal trends in incidence can only be partially explained by the HIV epidemic. In 1992, an international workshop sponsored by the United States National Cancer Institute concluded that there was an "emerging epidemic" of NHL and emphasized the need to investigate the factors responsible for the increasing incidence of this disease. Over the past two decades, numerous epidemiological studies have examined the risk factors for NHL, particularly for putative environmental and lifestyle risk factors, and international consortia have been established in order to investigate rare exposures and NHL subtype-specific associations. While few consistent risk factors for NHL aside from immunosuppression and certain infectious agents have emerged, suggestive associations with several lifestyle and environmental factors have been reported in epidemiologic studies. Further, increasing evidence has suggested that the effects of these and other exposures may be limited to or stronger for particular NHL subtypes. This paper examines the progress that has been made over the last twenty years in elucidating the etiology of NHL, with a primary emphasis on lifestyle factors and environmental exposures.
Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure–risk gradient. The fifth found a strong association and an exposure–response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case–control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes. Copyright © 2001 John Wiley & Sons, Ltd.
This chapter presents an overview of recent epidemiologic studies that address the association between atopic diseases and IgE and the risk of hematopoietic cancers, including a discussion of potential biological mechanisms. The strongest and most consistent (inverse) associations have been observed between allergic conditions and childhood leukemia, especially acute lymphoblastic leukemia. The cumulative evidence for an inverse association between atopy and non-Hodgkin lymphoma is suggestive, but the inconsistency of the associations with specific types of atopic conditions, the lack of any associations observed in most cohort studies, and the correlation between timing of diagnosis and decreasing IgE levels warrant further clarification. No consistent evidence has been found supporting an association between atopy and either plasma cell neoplasms or Hodgkin lymphoma.
There are several potential mechanisms by which allergic conditions could contribute to the risk of hematopoietic cancers. These include features of allergic responses (IgE, mast cell products) that may mediate enhanced antitumor immune responses, as well as allergy-associated changes in immune responses that inhibit immune cell activation, resulting in less exposure to DNA mutating and potentially oncogenic activities.
The International Agency for Research on Cancer has classified the evidence of a causal link between adiposity and human cancer
as “sufficient” for cancers of the colon, female breast (post-menopausal), endometrium, kidney (renal cell), and esophagus
(adenocarcinoma). In addition to these cancers, more recent epidemiological evidence suggests that cancers of the liver and
pancreas are obesity related, and that adiposity may also increase the risk for hematopoietic cancers and aggressive prostate
cancer. The mechanisms by which obesity is postulated to induce or promote tumorigenesis vary by site. These include insulin
resistance and resultant chronic hyperinsulinemia, increased bioavailability of steroid hormones, and localized inflammation.
The role that leptin, adiponectin, and other proteins secreted by adipocytes may have in the development and progression of
tumors is an active area of research.
The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood.
We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973-2008 who were followed for incidence of NHL through 2009 (ages 0-37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests.
There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥ 2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; P (trend) = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P (trend) = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL.
In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life.
The relationship between selected aspects of medical history and the risk of non-Hodgkin's lymphomas (NHLs) was investigated using data from a hospital-based case-control study conducted in northern Italy on 177 cases of NHL and 561 controls in hospital for acute conditions, other than nonneoplastic or immunological. Among six viral diseases considered, only herpes zoster (shingles) had a relative risk (RR) significantly above unity [RR = 2.7; 95% confidence intervals (CI), 1.5 to 4.7]. The association, however, was restricted to subjects whose diagnosis of herpes zoster dated back to less than 10 years, suggesting that this slow-acting virus could be reactivated by the early development of NHL. Six of eight bacterial diseases considered showed RR above unity, and the estimate was significant for scarlet fever (RR = 1.9; 95% CI, 1.1 to 3.5) and pyelonephritis (RR = 5.3; 95% CI, 1.8 to 16.2). These associations were not restricted to the few years before lymphoma diagnosis. When various classes of infectious or inflammatory diseases were grouped together, no association was evident for viral infections (RR = 0.8; 95% CI, 0.6 to 1.2), acute bacterial diseases (RR = 1.0; 95% CI, 0.7 to 1.5), or allergic conditions (RR = 1.0; 95% CI, 0.6 to 2.1). The risk estimates were nonsignificantly above unity for chronic bacterial diseases (RR = 1.2; 95% CI, 0.7 to 1.2) and autoimmune conditions (RR = 1.4; 95% CI, 0.9 to 2.2), and significantly elevated for chronic inflammatory disease (RR = 1.9; 95% CI, 1.2 to 3.0).(ABSTRACT TRUNCATED AT 250 WORDS)
The spatial distribution of new cases of lymphoma occurring in Yorkshire between 1978 and 1982 has been studied. Administrative districts were used as the basis for analysis and differences in age standardised incidence rates between districts were determined. Excessive rates for NHL were found to occur in Scarborough, York and Leeds districts. In addition an analysis contrasting broadly urban and rural districts showed an excess of NHL in rural areas, particularly of the follicular subtypes.
Indomethacin given continuously in the drinking water (20 micrograms/ml) to BALB/cAn pi mice during the latent period of pristane-induced plasmacytoma development dramatically reduced the plasmacytoma incidence from 34.9 to 2.2%. Additionally, indomethacin given from day 0 to 120 or begun as late as 60 d after a single injection of 1.0 ml pristane was also highly effective in reducing the development of plasmacytomas. Indomethacin treatment did not prevent the formation of a peritoneal inflammatory exudate or peritoneal oil granulomatous tissue, although it had a mild inhibitory effect on the intensity of the cellular inflammation, particularly after extensive treatment of greater than 100 d. Indomethacin treatment reduced the incidence of arthritis by 50%. A major effect of indomethacin treatment was a reduction in the appearance of microscopic plasmacytomas that appear in the oil granuloma before plasmacytomas can be detected by routine sampling of the peritoneal exudate. Between days 116 and 181, 16 of 20 mice given 0.5 ml pristane were found to have foci of plasmacytoma cells, while only 2 of 20 indomethacin-treated mice had foci-containing plasmacytoma cells. The number of mice with microscopic foci in the pristane-treated group greatly exceeded the expected incidence of plasmacytomas (22%) at this dose of pristane. The growth of primary plasmacytomas in transplant that is dependent on the pristane-conditioned peritoneal environment was not inhibited by indomethacin treatment. The role of indomethacin in inhibiting plasmacytoma development was not established; two possibilities are that it inhibits production of mutagenic and tissue destructive oxidants by inflammatory cells, and it inhibits prostaglandin synthesis and intracellular production of oxidant biproducts.
A number of serious infections, immunologic abnormalities and cancers have recently been reported in homosexual males. This syndrome, acquired immune deficiency syndrome (AIDS), was originally defined to include repeated infections with unusual opportunistic organisms and/or development of Kaposi's sarcoma (Friedman-Kien et al., 1981). Since the initial case descriptions, other manifestations of AIDS have been described, including malignant lymphomas of B lymphocytes (Ziegler et al., 1982). These lymphomas have usually been described histologically as immunoblastic sarcomas (IBS) or small non-cleaved follicular centre cell lymphomas, both Burkitt and non-Burkitt types. Since 1982, we have observed at our institution 27 cases of non-Hodgkin's lymphomas in homosexual men, 22 of which were diagnosed with one of the high-grade histologic types. To date, it has not been shown systematically whether the association of lymphoma and homosexuality is coincidence or represents an excess over what would be expected by chance. Using incidence data from our population based tumour registry of Los Angeles County, we have been able to monitor this purported epidemic of malignant lymphoma and determine its magnitude.
Although random digit dialing (RDD) is an accepted and commonly used method of sampling populations for controls in case-control studies, there have been surprisingly few attempts to compare the accuracy of RDD with that of the best traditional alternative, i.e., household area surveys. The aim of the present study was to compare a variety of characteristics of control subjects selected by ROD and area survey methods. All data were gathered through in-person interviews of both types of control subjects. The area survey identified a population-based sample of 20- to 79-year-old residents of two Washington State counties in 1978 and 1979. Control groups for three case-control studies of bladder cancer, gynecologic cancers, and multiple myeloma were drawn from this area sample, for a total of 240 control subjects. Controls aged 21-64 years from the same counties were identified for the National Bladder Cancer Study using ROD telephone sampling during the same time period. There were 134 respondents in the ADD control group. Overall, the two control groups selected by these two different methods yielded similar estimated frequencies of various population characteristics. The small differences observed in some age/sex subgroups and the statistical significance of the overall measure of association for occupational exposure to organic substances may be attributed to multiple compar isons.
A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.9, 2.6). Relative risk of NHL increased significantly with number of days of herbicide exposure per year and latency. Men exposed to herbicides more than 20 days per year had a sixfold increased risk of NHL (OR, 6.0; 95% CI, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% CI, 2.3, 27.9) for NHL. Excesses were associated with use of phenoxyacetic acid herbicides, specifically 2,4-dichlorophenoxyacetic acid. Neither STS nor HD was associated with pesticide exposure. This study confirms the reports from Sweden and several US states that NHL is associated with farm herbicide use, especially phenoxyacetic acids. It does not confirm the case-control studies or the cohort studies of pesticide manufacturers and Vietnam veterans linking herbicides to STS or HD.
(JAMA 1986;256:1141-1147)
Indomethacin given continuously in the drinking water (20 micrograms/ml) to BALB/cAn pi mice during the latent period of pristane-induced plasmacytoma development dramatically reduced the plasmacytoma incidence from 34.9 to 2.2%. Additionally, indomethacin given from day 0 to 120 or begun as late as 60 d after a single injection of 1.0 ml pristane was also highly effective in reducing the development of plasmacytomas. Indomethacin treatment did not prevent the formation of a peritoneal inflammatory exudate or peritoneal oil granulomatous tissue, although it had a mild inhibitory effect on the intensity of the cellular inflammation, particularly after extensive treatment of greater than 100 d. Indomethacin treatment reduced the incidence of arthritis by 50%. A major effect of indomethacin treatment was a reduction in the appearance of microscopic plasmacytomas that appear in the oil granuloma before plasmacytomas can be detected by routine sampling of the peritoneal exudate. Between days 116 and 181, 16 of 20 mice given 0.5 ml pristane were found to have foci of plasmacytoma cells, while only 2 of 20 indomethacin-treated mice had foci-containing plasmacytoma cells. The number of mice with microscopic foci in the pristane-treated group greatly exceeded the expected incidence of plasmacytomas (22%) at this dose of pristane. The growth of primary plasmacytomas in transplant that is dependent on the pristane-conditioned peritoneal environment was not inhibited by indomethacin treatment. The role of indomethacin in inhibiting plasmacytoma development was not established; two possibilities are that it inhibits production of mutagenic and tissue destructive oxidants by inflammatory cells, and it inhibits prostaglandin synthesis and intracellular production of oxidant biproducts.
The association between farming occupations and the incidence of non-Hodgkin's lymphoma (NHL) was examined in a case-control study using a cancer registry to identify cases and controls and death certificates to determine the occupation and industry of employment of cancer patients. Case subjects were white males with a diagnosis of NHL who died between 1967 and 1982; control subjects were white males who died of colon cancer during the same period. Control and case subjects were frequency-matched for age and year of diagnosis; county of residence was not a matching variable. Death certificates with codable occupational information were located for 90% of the 249 case and 293 control subjects. A stratified analysis using test-based confidence intervals revealed an increased risk of NHL among farmers. The overall odds ratio, controlling for age and for year of diagnosis, was 1.3 (90% confidence limits 0.9-2.3). For diagnoses during 1952 through 1965, the odds ratio was 6.6, and for diagnoses during 1966 through 1971, the odds ratio was 3.1. The increased odds ratio was most pronounced among those aged 45 to 64 years at the time of diagnosis and those living in rural counties. (C)1985 The American College of Occupational and Environmental Medicine
We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.
(JAMA 1985;254:1921-1925)
In 1982, Helicobacter pylori was isolated from the human stomach for the first time.64 Since then, it has garnered considerable interest. In 1996, according to one computer database, more papers were published on H. pylori than on any other enteric pathogen. At the 1997 United States Gastroenterology Conference (Digestive Diseases Week), more than 500 presentations related to clinical, epidemiologic, pathophysiologic or microbiologic aspects of this organism. The emergence of H. pylori into clinical consciousness, however, belies what is happening to the organism itself. Epidemiologic studies indicate that H. pylori infection is decreasing in prevalence, at least in the industrialized West. Moreover, the diseases attributed to H. pylori infection, peptic ulcer disease and gastric malignancy, are declining in parallel with infection; however, despite these decreases, H. pylori remains an important cause of morbidity and mortality throughout the world. Peptic ulcer disease continues to affect millions annually, and gastric cancer is among the top few causes of cancer death worldwide. Thus, the extraordinary attention devoted to this curable and perhaps preventable infection appears well warranted.
In the immune system, histamine is known to suppress cytotoxic T-lymphocytes and mitogen induced lymphocyte thymidine uptake, down-regulate some cytokines, and activate suppressor T-lymphocytes, and in the gastrointestinal system, histamine was reported to have trophic effects on gastrointestinal epithelial cells. Enhanced rates of cell proliferation by histamine are implicated in the pathogenesis of carcinogenesis. This study was designed since there is a lack of comparative data about the cell proliferations of histamine-2 receptor antagonist (H2-RA), cimetidine, ranitidine, and famotidine, in gastric cancer. KATO-III and AGS cell lines were used in this experiment. The concentrations of the histamine and cimetidine were 10−5, 10−8M, respectively and those of ranitidine and famotidine were 10−6-10−9M, respectively. Cell proliferation after drug treatment was evaluated by direct cell counting, [3H]thymidine incorporation, and MTT assay. Activities of ornithine decarboxylase (ODC), a rate limiting enzyme in polyamine synthesis, were measured after each drug treatment. Protein kinase A, a cAMP-dependent protein kinase system, was assayed using [α-32p]ATP. Histamine showed statistically significant cell proliferating effects in a dose-dependent manner (P < 0.01), the maximal effect in 10−5M concentration. ODC activities were increased in accordance with the increment of cell numbers after histamine treatment. Cimetidine reversed the histamine-stimulated cell proliferation significantly, the maximal effect in 10−5M concentration (P < 0.01). Although ranitidine showed the tendency to attenuate the cell proliferation dose-dependently, but without statistical significance, famotidine did not show such an effect at all. cAMP-dependent protein kinase activities were significantly increased following 10−5M histamine treatment, also reversed significantly by cimetidine co-administration (P < 0.01). Beneficial clinical outcomes could be anticipated from cimetidine treatment in patients with gastric cancer by anti-proliferating effects against gastric cancer cells. These effects of H2-RA are likely to be mediated by specific interactions at the H2-receptor.
In rodents, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin inhibit chemically induced adenomas and early carcinomas of the colon. The NSAID Sulindac inhibits the growth of polyps of the colon and rectum in two randomized trials of patients with familial adenomatous polyposis (FAP), although the inhibition is not complete. Eight epidemiologic studies have found a 40-50% reduction in polyps or colorectal cancer among persons who regularly use aspirin or other NSAIDs compared to those who do not. Two epidemiologic studies show a slight increase in risk. Interpretation of the epidemiologic studies is complicated, because bleeding induced by aspirin may enhance the diagnosis and early treatment of cancer, and at least in theory, the symptoms of cancer could cause patients to avoid aspirin. Clinical trials designed specifically to investigate the aspirin hypothesis in humans at high risk of colorectal polyps or cancer are needed to establish causality, and to define the optimal dose and drug. Experimental studies should further define the mechanism of tumor inhibition in animals.
The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkin's lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenström's macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.
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.
A very large proportion of non-Hodgkin's lymphoma in the United States are of B-cell origin. This group of tumors includes a variety of different pathological and clinical types. Chromosomal rearrangements play an important role in the pathogenesis of many of these tumors. In B-cells these translocation processes appear to develop as illegitimate products of physiological V-(D)-J or heavy chain switch rearrangements. The biology of the well-known chromosomal translocations is discussed. Additional biological factors in lymphomagenesis (aging, immunodeficiency, role of antigenic stimulation, and genetically determined susceptibility) are discussed.
To determine whether non-Hodgkin's lymphoma (NHL) is related to prior medication use or health history, a population-based case-control study was conducted. A total of 619 male and female residents of Los Angeles County who were diagnosed with NHL between January 1, 1979, and June 30, 1982, were compared to individually age-, race-, and sex-matched neighborhood controls with regard to history of use of 49 different medications, 47 chronic and infectious diseases or other conditions, 15 types of immunizations, and 15 specific allergic reactions. Based on preliminary analyses, long-term regular use of aspirin and other pain relievers and greater than or equal to 2 mo of treatment with penicillin and other antibiotics were associated with significantly increased risk of NHL. Other drugs associated with greater risk of NHL were use of digitalis and estrogen replacement therapy by women, use of corticosteroids, and greater than or equal to 2 mo of use of tranquilizers. NHL was strongly associated with a prior history of cancer. Cases more frequently reported histories of kidney infections and anemia than did controls; a history of eczema appeared to be protective against NHL. Women who had been immunized against polio by injectable vaccine were at significantly lower risk of NHL than women who had not received this immunization. Among men, cholera immunization and allergy to nuts and berries were significantly protective. Subjects who had received a yellow fever immunization also had lower NHL risk. Further analyses of these data will attempt to establish the relative importance of these potential risk factors and to determine whether any are markers of early symptoms of NHL.
Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors.
Rheumatoid arthritis (RA) represents the autoimmune disease that has been most studied in relation to malignancy. An examination of all published cohort studies has indicated a 9.7-fold increase of non-Hodgkin's lymphoma among RA patients after immunosuppressive therapy, and a 2.5-fold increase in the absence of such treatment. Corresponding data for Sjögren's syndrome point to a similar contrast. These findings are inseparable from the hypothesis of impaired immunosurveillance which implies that malignancy is promoted by defects in the immune system. Studies of individuals treated with immunosuppressive drugs, particularly to prevent graft rejection, have indicated that immunosurveillance operates only against a restricted range of neoplasms. These include non-Hodgkin's lymphoma (NHL), squamous cell skin cancer, Kaposi's sarcoma and cervical carcinoma. Other states of immune impairment including AIDS are also associated with marked increases of NHL. There is a striking correspondence between malignancies for which there is epidemiological or laboratory evidence for a virus aetiology and those that are increased by immune impairment. In this respect the epidemiological evidence accords with experimental work that immunosurveillance primarily operates against neoplasms of viral origin. It is therefore possible that a viral aetiology also underlies the excess of NHL in certain autoimmune disorders, particularly after immunosuppressive therapy.
The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.
Intraperitoneal (i.p.) injection of a mineral oil such as pristane induces a chronic inflammatory response in mice. This is characterized by a large influx of macrophages and other inflammatory cells into the peritoneal cavity for months after injection of the oil. By using the B9 cell bioassay, it was found that injection of pristane caused a marked and prolonged elevation of interleukin-6 (IL-6) levels in the peritoneal cavities of the mice. IL-6 was undetectable (less than 15 U/mL) in the peritoneal fluids of unprimed mice and during the first week after injecting pristane. From 4 to 20 weeks, the concentration of IL-6 increased to an apparent plateau with concentrations ranging from 200 to 2,000 U/mL. Increasing the dose of pristane did not substantially increase the peritoneal levels of IL-6 established at 20 weeks after pristane treatment. At later times (by day 250), the level decreased to 263 +/- 217 U/mL. However, mice that developed plasma cell tumors around day 300 showed high levels of IL-6 in the ascites fluid (650 to 2,400 U/mL). Serum levels of IL-6 were also elevated in pristane-primed mice but were substantially lower than those found in the peritoneal cavity. Chronic administration of the nonsteroidal anti-inflammatory drug indomethacin decreased the levels of IL-6 by 75% to 80%. Experiments performed in vitro showed that pristane-elicited macrophages secreted low levels of IL-6 constitutively and high levels of IL-6 in the presence of lipopolysaccharide. Both IL-6 and prostaglandin E2 production were inhibited by addition of indomethacin to macrophage cultures in vitro. Treatment of mice with pristane may provide a model system for studying the inflammatory pathways that control IL-6 levels in vivo. The relevance of these results to elucidation of the role of IL-6 in plasma cell tumorigenesis is discussed.
Direct studies linking drugs of abuse with changes in neurotransmitters and subsequent effects on the immune system are not abundant. One can, however, hypothesize that an indirect effect can occur since a variety of neurotransmitters known to be acted on by various drugs of abuse can, in turn, be correlated with changes in immunity. These changes most likely are mediated via alterations in the autonomic nervous system or the ratio of hormones regulated by the pituitary gland. In addition, there is sound evidence to suspect that the immune system might be capable of altering either the induction of tolerance or the severity of withdrawal symptoms. An increasing body of evidence indicates that IL-1, IFN-alpha, as well as C3a and C5a of the complement cascade, are capable of acting on central catecholamines within the brain. The possibility that immune system peptides are capable of regulating neurotransmitters is further suggested by the evidence of neuropsychiatric side effects during the course of clinical trials. Since a variety of drugs of abuse can directly alter immunocompetence as evidenced by the results of in vitro protocols described elsewhere in this volume, one could speculate that certain behavioral manifestations of drug addiction may be modulated, in part, by immunologic status.
The relationship between selected aspects of medical history and the risk of colorectal cancer was analysed using data from a case-control study of 673 cases of colon cancer, 405 of rectal cancer and 1501 controls in hospital for acute, non-neoplastic, non-digestive tract conditions, unrelated to known or suspected risk factor for large bowel cancer. Significantly elevated risks (RR) were observed for history of cholelithiasis (RR = 1.5 [95% confidence interval (CI) 1.1-2.1] for colon; 1.6 [1.2-6.4] for rectum) and diabetes (1.6 [1.1-2.3] for colon; 1.3 [0.8-2.0] for rectum), and a significant protection emerged for history of drug allergy (0.6 [0.4-0.9] for colon; 0.6 [0.5-1.0] for rectum). No significant association was found with thyroid disease, gastroduodenal ulcer, liver cirrhosis, hepatitis, pancreatitis, gastrectomy, appendicectomy, treatment with cimetidine/ranitidine, treatment with chenodesoxycholic acid or with blood transfusions. The associations with cholelithiasis, diabetes and drug allergy were not materially modified by allowance for major identified potential confounding factors, and were not restricted to the diseases diagnosed within 5 or 10 years before large bowel cancer diagnosis. Thus, the analysis of this large dataset offered further quantitative evidence suggesting a possible, however moderate, association between gallbladder disease and colorectal cancer risk, which may be related to enhanced or continuous secretion of secondary bile acids. The associations with diabetes and drug allergy were unexpected, and probably indirect, lacking previous epidemiological support or any obvious biological interpretation. Thus, they should be simply regarded as working hypotheses worthy of further consideration.
Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.
Components in the insect venom and probably also in their saliva may have direct toxic effects or may cause sensitization and may result in allergic reactions to subsequent stings. In Denmark, only the stings of honey bees and wasps (yellow jackets) are of clinical significance and it is important to be aware that these insects contain separate allergenic components. Clinical manifestations following stings are observed from all of the organ systems on the whole. The commonest are itching of the skin, urticaria, possibly angioedema and slight generalized symptoms with vertigo, headache and fatigue. Life-threatening reactions may also occur and one or two fatal cases are registered annually in Denmark. It may be difficult to decide whether an allergic or a toxic reaction is involved on the basis of the symptoms. Possible IgE-sensitization must therefore be assessed by means of a prick test and measurement of specific IgE. The main treatment in cases of acute systemic reactions is adrenaline which may possibly be supplemented with antihistamine and corticosteroid. In cases of massive local reactions and urticaria, antihistamines will, as a rule, prove sufficient. Hyposensitization with insect venom preparations eliminates the future risk for systemic insect sting reactions practically entirely and this must be recommended for patients with demonstrated IgE-sensitizing and generalized reactions. At present, treatment should be continued for three to five years and protection lasts for a series of years after cessation of treatment.
Blood histamine proved to be important for the immune homeostasis. By its direct action or by means of H-2 receptors it end or prevents the excessive immune response. Recent studies revealed changes in cell mediated immunity in subjects with atopia, with increased histaminemia and their obvious protection against cancer. In patients with cancer, hypogammaglobulinemia, AIDS, the depression of the immune responses was partly accounted for by the decrease of blood histamine and by the change of the number of H-2 receptors. Hence the attempt to treat these diseases with H-2 antagonists associated or not with histamine.
An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B-lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B-cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non-Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients.
Severe immunodeficiency diseases are complicated by the development of malignancies of the immune system itself, mainly non-Hodgkin's lymphoma (NHLs). These occur in immunosuppressed organ allograft recipients; in cancer chemotherapy patients; in patients with primary immunodeficiency diseases; in chronic dialysis patients; in victims of the Acquired Immunodeficiency Syndrome (AIDS); and in persons with various autoimmune diseases either untreated or given immunosuppressive therapy. Most of these NHLs are reticulum cell sarcomas or immunoblastic sarcomas. Immunologically, most are of B-cell origin. Most tumors are extranodal in distribution. They show a remarkable predilection for the brain. Possible causes of the NHLs include oncogenic viruses; disturbed immune surveillance; chronic antigenic stimulation; impaired immunoregulation; carcinogenic effects of immunosuppressive, cytotoxic or other drugs; and genetic susceptibility to lymphomagenesis.
The role of various life style factors, including dietary habits, in the etiology of non-Hodgkin's lymphoma was investigated using data from a case-control study conducted in the northeastern part of Italy. This study was done on 208 histologically confirmed non-Hodgkin's lymphomas and 401 control subjects who were in the hospital for acute, nonimmunologic, or neoplastic conditions. Dietary histories concerned the frequency of consumption per week of alcohol, beverages that contain methylxanthine, and 14 select food items or groups of foods (including major sources of proteins, fat, fibers, and vitamin A in the Italian diet). The consumption of milk, liver, butter, oil (chiefly polyunsaturated oils), coffee, tea, and cola was positively related with non-Hodgkin's lymphoma risk. the consumption of whole-grain bread and pasta showed a protective effect. When a logistic model was fitted that included the aforementioned food items in addition to major nondietary covariates, all of the foods, except liver and beverages that contain methylxanthine, remained significant. Interestingly, these associations are in agreement with the positive correlation that is emerging internationally between the consumption of fat and proteins and non-Hodgkin's lymphoma.
The ability of husbands' sperm to inhibit proliferation of their wives' lymphocytes was measured. Seventeen of 27 sperm samples tested (63%) inhibited lymphocytes from responding to Candida antigens. Eleven of the 27 women (41%) had sera that were positive for antisperm antibodies; sperm from only four of their husbands (36%) were immunosuppressive. In contrast, 13 of the 16 women (81%) without antisperm antibodies had partners with suppressive sperm. Lymphocytes from four women with antisperm antibodies were inhibited by sperm from a fertile donor although not inhibited by their husband's sperm, whereas in three other antibody-positive women neither the husbands' nor donors' sperm were inhibitory. Antisperm antibodies in some women may arise as a consequence of a failure of sperm from their male partners to inhibit lymphocyte activation.
We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.
Aggregation of exposures in cases of non-Hodgkin's lymphomas was brought to our attention when an astute person reported the unusual occurrence of what she believed to be Burkitt's lymphoma in four adult members of a family in the United States after they shared an exposure to an ill visitor from Africa. We report the results of an epidemiologic and laboratory investigation of this aggregation. Our findings suggest that it may have been caused by an unidentified transmissible agent.
Allergy prick skin testing was performed on 137 newly diagnosed patients with primary lung cancer and 137 age-(+/- 3 years) and sex-matched randomly selected control subjects. We also compared 38 patients with lung cancer and 38 of their closest in age, same-sex siblings. Demographic data, personal, medical, smoking and occupational histories were obtained by personal interview. We skin tested these individuals with a standard battery of seven common allergens and a diluent control. Fewer patients (35.8 percent) than control subjects (58.4 percent) responded with one or more positive skin reactions (p less than .005). There was no significant difference between patients (27.8 percent) and control subjects (37.2 percent) responding to more than one allergen. Fewer of the 38 sibling-matched patients had one or more positive skin tests (23.7 percent) than did their siblings (55.3 percent) (p less than .01). There were fewer patients with greater than one positive skin test (15.8 percent) than sibling control subjects (42.1 percent) (p less than .025). There were no differences in smoking pack-years between patients and siblings. Historic evidence of allergy was greater in both control groups compared to their matched cancer groups; p less than .05 for community controls, p less than .005 for sibling control subjects. These findings raise the possibility that atopy, by either immunologic or nonimmunologic means, protects against development of lung cancer, or alternately, that lung cancer affects immunologic status as gauged by (type 1) skin sensitivity.
This paper reports the results of a case control study of non-Hodgkin's lymphoma in the Yorkshire Health Region. In all, 437 cases and 724 controls were interviewed. Risk factors associated with past skin conditions, family history of cancer and infectious mononucleosis, aspects of social life and contact with wood dust and epoxy glues all emerge. A comparison of high and low grade morphological forms of disease reveal contrasting risks and suggest separate aetiologies for these conditions.
Annual incidence rates for 1975-1985 were derived for Kaposi's sarcoma, non-Hodgkin's lymphomas, and seven other malignancies. Never-married men in the San Francisco Bay area constituted the study population. The pattern of increase in incidence of non-Hodgkin's lymphoma among men aged 25-44 years was similar to that seen for Kaposi's sarcoma; both increased significantly in San Francisco between 1980 and 1985 (p less than 0.001), with an increase among census tracts with high incidence of acquired immunodeficiency syndrome (AIDS) that was greater than the increase seen in other San Francisco census tracts. Among men in tracts with a high incidence of AIDS, non-Hodgkin's lymphoma reached an incidence in 1985 that was five times greater than preepidemic rates. These increased rates support the conclusion of clinical studies that non-Hodgkin's lymphoma is an additional manifestation of AIDS. Similar increases in incidence rates were not observed for other malignancies, suggesting that reports of these malignancies in homosexuals may be isolated incidents. Whether rates of non-Hodgkin's lymphoma will continue to increase and whether rates of other potentially AIDS-associated malignancies will increase in the future may depend on the latency of these malignancies and the survival period of AIDS patients.
A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.9, 2.6). Relative risk of NHL increased significantly with number of days of herbicide exposure per year and latency. Men exposed to herbicides more than 20 days per year had a sixfold increased risk of NHL (OR, 6.0; 95% CI, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% CI, 2.3, 27.9) for NHL. Excesses were associated with use of phenoxyacetic acid herbicides, specifically 2,4-dichlorophenoxyacetic acid. Neither STS nor HD was associated with pesticide exposure. This study confirms the reports from Sweden and several US states that NHL is associated with farm herbicide use, especially phenoxyacetic acids. It does not confirm the case-control studies or the cohort studies of pesticide manufacturers and Vietnam veterans linking herbicides to STS or HD.
A case-control study was undertaken to determine whether a prior history of a variety of acquired disorders affecting the immune system was associated with an increased risk of non-Hodgkin's lymphoma. Cases were identified over a 4-year period (1976-1979) at the Johns Hopkins Hospital and individually matched to hospital controls on age, sex, race, and year of diagnosis. For the 109 cases and matched controls who were traced and interviewed, positive associations suggesting an increase in risk were not detected. Instead, there was a suggestion of an inverse relationship. Odds ratios (ORs) were consistently less than 1 for associations between non-Hodgkin's lymphoma and several chronic infectious diseases (OR = 0.65, 95% CI = 0.35, 1.20), chronic inflammatory diseases (OR = 0.88, 95% CI = 0.43, 1.79), autoimmune disorders (OR = 0.80, 95% CI = 0.19, 3.76), and allergic disorders (OR = 0.77, 95% CI = 0.45, 1.32). A statistically significant protective association was found for surgical removal of lymphoid tissue (OR = 0.50, 95% CI = 0.27, 0.91). Adjustment for potentially confounding variables did not change these results. These findings do not support the previously anecdotally reported impression that disorders producing a chronic antigenic stimulus are associated with the development of non-Hodgkin's lymphoma.
Physical and social characteristics recorded at college physical examination and reported in subsequent questionnaires to alumni in 1962 or 1966 by 50,000 former students from Harvard University and the University of Pennsylvania were reviewed for their relationship to major site-specific cancer occurrence. The records of 1,359 subjects who died with a major site-specific cancer in a 16- to 50-year follow-up period and of 672 subjects who reported such a cancer by mail questionnaire in 1976 or 1977 were compared with those of 8,084 matched classmates who were known to be alive and free of cancer at the time subjects with cancer had died or had been diagnosed. Cigarette smoking, as reported both in student years and years as alumni, predicted increased risk for cancers of the respiratory tract, pancreas, and bladder. Student coffee consumption was associated with elevated risk for leukemia, but it was unrelated to cancers of the pancreas and bladder. Male students with a record of proteinuria at college physical examination experienced increased risk of kidney cancer, and those with a history of tonsillectomy experienced increased risk of prostate cancer. Students who at college entrance reported occasional vague abdominal pain were at elevated risk for pancreatic and colorectal cancers in later years. Increased body weight during college was associated with increased risks of kidney and bladder cancers, whereas for alumni this index was associated only with kidney cancer. Increased weight-for-height during college (but not in 1962 or 1966) predicted increased occurrence of female breast cancer. Jewish students experienced elevated risk for subsequent cancers of the female breast, colon, and combined colorectum. These and other findings are presented as clues deserving further exploration for any etiologic significance that they may hold for the cancer sites studied.
The association between farming occupations and the incidence of non-Hodgkin's lymphoma (NHL) was examined in a case-control study using a cancer registry to identify cases and controls and death certificates to determine the occupation and industry of employment of cancer patients. Case subjects were white males with a diagnosis of NHL who died between 1967 and 1982; control subjects were white males who died of colon cancer during the same period. Control and case subjects were frequency-matched for age and year of diagnosis; county of residence was not a matching variable. Death certificates with codable occupational information were located for 90% of the 249 case and 293 control subjects. A stratified analysis using test-based confidence intervals revealed an increased risk of NHL among farmers. The overall odds ratio, controlling for age and for year of diagnosis, was 1.3 (90% confidence limits 0.9-2.3). For diagnoses during 1952 through 1965, the odds ratio was 6.6, and for diagnoses during 1966 through 1971, the odds ratio was 3.1. The increased odds ratio was most pronounced among those aged 45 to 64 years at the time of diagnosis and those living in rural counties.
This paper presents the results of a retrospective study that examines the association of cancer with a history of asthma, hay fever, hives, and other allergy-related diseases. This study is based on interview data collected from 13,665 cancer cases and 4,079 nonneoplastic controls who were admitted to Roswell Park Memorial Institute from 1957 to 1965. Although there is a general tendency for the age- and cigarette smoking-adjusted odds ratios associated with a history of asthma and hay fever to be less than 1, for both males and females, there is stronger evidence for a decreased risk of cancer associated with a history of hives and other allergy-related diseases. Decreased risks associated with a history of hives and other allergies are seen in males for oral cancer, cancers of the lung, larynx, digestive system, urinary system, and cancers of all sites combined and in females for cancers of the digestive system, reproductive system, in particular, cancer of the cervix, and cancers of all sites combined. None of the few odds ratios over 1 associated with a history of any allergy-related condition are statistically significant (alpha = 0.05). These findings suggest that individuals with allergy-related disorders may be at decreased risk of cancer, although reasons for cautious interpretation of the findings are emphasized. Prospective studies of carefully defined allergic disease cohorts are needed.
Four cases of Burkitt's-like lymphoma (undifferentiated, monoclonal, B-cell tumours) in homosexual men were seen in a 9-month period in San Francisco. One tumour contained both Epstein-Barr-virus nuclear antigen (EBNA) and cytomegalovirus (CMV) antigen. Another tumour contained EBNA, and a third contained no viral antigen, but EBNA and CMV antigens were detected in the overlying epithelium. This outbreak widens the array of neoplasms affecting immunosuppressed homosexual men and provides further evidence of an oncogenic role for EBV and CMV.
An epidemiological case-control study of non-Hodgkin's lymphomas revealed an excess of male patients with large-cell lymphomas primary to the gastrointestinal tract and oral cavity who had evidence of substantial exposure to asbestos. Between 1977 and 1981, 28 men with large-cell lymphomas primary to these sites were interviewed about previous environmental exposure. Pathology slides from 26 of these cases were reviewed by haematopathologists, who confirmed each to be non-Hodgkin's lymphoma of large-cell type. Neighbourhood controls were matched to patients for age, race, and sex. 13 matched pairs were discordant for asbestos exposure, and in 12 of these the exposed individual was a lymphoma patient. 10 patients and 1 control also reported a history of malaria.
Results are described from four epidemiologic studies in the United States which used random digit dialing in over 30,000
households to identify controls from the general population for use in case-control studies. Methods and problems in telephone
sampling are discussed. It Is concluded that if complete population rosters are unavailable and if the population to be sampled
has the high rates of telephone ownership typical of much of the United States, telephone-based sampling can yield a nearly
random sample of the individuals in a population, often at much less expense than can dwelling-based sampling.
Serious infections, neoplasms, and immunologic abnormalities have been found in homosexual men. We describe the development of malignant lymphoma in six such patients, three of whom had persistent, generalized lymphadenopathy. In biopsies done before the lymphoma developed, the lymphadenopathy was characterized morphologically by a distinctive pattern of B-cell follicular hyperplasia. All lymphomas were of B-lymphocytic origin, including B-cell immunoblastic sarcoma; small noncleaved, Burkitt-like lymphoma; and plasmacytoid lymphocytic lymphoma. Extranodal presentation with B symptoms occurred in five patients. Median age of our patients was 33 years. Three patients had histories of repeated systemic infections. The peripheral blood lymphocyte count was depressed in four, with depression of OKT 4+ (helper phenotype) cell levels and reversal of the T-helper: T-suppressor ratio in all. We conclude that these patients are at risk for the development of abnormalities of the B-lymphocytic system, manifested by abnormal hyper-B-cell response in enlarged reactive lymph nodes and aggressive, extranodal B-cell lymphomas.
Weekly deposition of pooled rabbit semen into the rectum in healthy male rabbits resulted in the appearance of immune complexes and antibodies to sperm and to peripheral blood lymphocyte antigens. It also led to a decreased ability to mount a humoral immune response to T lymphocyte-dependent antigens, keyhole limpet hemocyanin, and sheep red blood cells. These findings suggest that repeated rectal deposition of semen may compromise some aspects of the immune system.
We describe the histologic and clinical features of non-Hodgkin's lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposi's sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkin's lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.