Publications (62)274.1 Total impact
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Article: Plasma adiponectin levels and endometrial cancer risk in pre-and postmenopausal women
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ABSTRACT: Background: Adiponectin, an adipocytokine secreted by adipose tis-sue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk fac-tors for endometrial cancer.Epidemiology Unit (F.Be.), Istituto Nazionale Tumori Cancer Registry Julius Center for Health Sciences and Primary Care The Netherlands Clinical Gerontology. ; 69372(3508). -
Article: Latitude and ultraviolet radiation dose in the birthplace in relation to menarcheal age in a large cohort of French women.
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ABSTRACT: BACKGROUND: Age at menarche is an important determinant of hormonal-related neoplasia and other chronic diseases. Spatial and temporal variations in age at menarche have been observed in industrialised countries and several environmental factors were reported to have an influence. Method We examined geographical variations in self-reported age at menarche and explored the effects of both latitude and ultraviolet radiation (UVR) dose on the onset of menarche in 88 278 women from the French E3N cohort (aged 40-65 years at inclusion). RESULTS: The mean age at menarche was 12.8 years. After adjustment for potential confounders (birth cohort, prematurity, birth weight and length, father's income index, body silhouette in childhood, food deprivation during World War II, population of birthplace, number of siblings, breastfeeding exposure and indoor exposure to passive smoking during childhood), latitude and UVR dose (annual or spring/summer) in county of birth were significantly associated with age at menarche (Ptrend < 0.0001). Women born at lower latitudes or in regions with higher annual or spring/summer UVR dose had a 3- to 4-month earlier menarche than women born at higher latitudes or in regions with lower UVR. On a continuous scale, a 1° increment in latitude resulted in a 0.04-year older age at menarche [95% confidence interval (CI): 0.03, 0.05], whereas a 1-kJ/m(2) increment in annual UVR dose resulted in a 0.42-year younger age at menarche (95% CI: -0.55, -0.29). CONCLUSION: These data further suggest that light exposure in childhood may influence sexual maturation in women.International Journal of Epidemiology 04/2013; 42(2):590-600. · 6.41 Impact Factor -
Article: Plasma 25(OH)vitamin D and the risk of breast cancer in the european prospective investigation into cancer and nutrition (EPIC): A nested case-control study.
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ABSTRACT: Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. While the results of case-control studies indicate that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1391 incident breast cancer cases and 1391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4- Q1 [95% CI]: 1.07 [0.85-1.36], ptrend =0.67). Moreover, 25(OH)D levels were not related to the risks of ER+ tumors (ORQ4- Q1 [95% CI]: 0.97 [0.67-1.38], ptrend =0.90) and ER- tumors (ORQ4- Q1 [95% CI]: 0.97 [0.66-1.42], ptrend =0.98). In HRT users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p=0.01), whereas no significant association was found in HRT non-users (ORlog2 [95% CI]: 1.14 [0.80-1.62], p=0.48). Further, a non-significant inverse association was found in women with BMIs <25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p=0.09), as opposed to a borderline significant positive association in women with BMIs ≥25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p=0.05). Overall, pre-diagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer. © 2013 Wiley Periodicals, Inc.International Journal of Cancer 03/2013; · 5.44 Impact Factor -
Article: Hormonal, Metabolic, and Inflammatory Profiles and Endometrial Cancer Risk Within the EPIC Cohort--A Factor Analysis.
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ABSTRACT: A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.American journal of epidemiology 03/2013; · 5.59 Impact Factor -
Article: Anthropometric characteristics and risk of lymphoid and myeloid leukemia in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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ABSTRACT: PURPOSE: Overweight and obesity have been suggested as a risk factor for leukemia. Impaired immune function associated with obesity, increased insulin-like growth factor-I activity and stimulating effects of leptin suggest a possible biological link between anthropometric measures and leukemia. However, evidence from epidemiological studies has been inconsistent. We examined the potential association between prospective measurements of body size and risk of leukemia among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: During follow-up (mean = 11.52 years, standard deviation = 2.63), 671 leukemia (lymphoid leukemia = 50.1 %, myeloid leukemia = 43.2 %) cases were identified. Anthropometric measures including weight, height, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-hip ratio (WHR) were measured. Cox proportional hazard models were used to explore the association between anthropometric measures and risk of leukemia. RESULTS: No associations were observed between anthropometric measures and total leukemia, and lymphoid leukemia. Risk of myeloid leukemia significantly increased for higher categories of BMI and WC among women. Analyses by subtype of myeloid leukemia showed an increased risk of acute myeloid leukemia (AML) for higher categories of WHR among women. This association seemed to be reversed for chronic myeloid leukemia. No association between anthropometric measures and myeloid leukemia were observed among men except an increased risk of AML with height. CONCLUSION: The study showed no associations between anthropometric measures and total leukemia, and lymphoid leukemia among men and women. A possible association between BMI as general obesity and WC as abdominal obesity and increased risk of myeloid leukemia among women were observed.Cancer Causes and Control 01/2013; · 2.88 Impact Factor -
Article: Alcohol drinking and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
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ABSTRACT: PURPOSE: Alcohol intake may adversely affect the concentrations of endogenous sex hormones, and thus increase the risk of endometrial cancer. However, epidemiologic studies have provided conflicting results. Therefore, we investigated the association between alcohol intake and endometrial cancer risk a large, multicenter, prospective study. METHODS: From 1992 through 2010, 301,051 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed for incident endometrial cancer (n = 1382). Baseline alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. RESULTS: The multivariable HRs (and 95% CIs) compared with light drinkers (0.1-6 g/d) were 1.03 (0.88-1.20) for 0 g of alcohol per day at baseline, 1.01 (0.86-1.17) for 6.1-12 g/d, 1.03 (0.87-1.22) for 12.1-24 g/d, 1.07 (0.87-1.38) for 24.1-36 g/d, and 0.85 (0.61-1.18) for more than 36 g/d (p(trend) = 0.77). No association was observed among former drinkers (OR, 1.28; 95% CI, 0.98-1.68 compared with light drinkers). Null associations were also found between alcohol consumption at age 20 years, lifetime pattern of alcohol drinking, and baseline alcohol intake from specific alcoholic beverages and endometrial cancer risk. CONCLUSIONS: Our findings suggest no association between alcohol intake and endometrial cancer risk.Annals of epidemiology 12/2012; · 2.95 Impact Factor -
Article: North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.
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ABSTRACT: Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (P trend < 0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (P trend < 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.The British journal of nutrition 12/2012; · 3.45 Impact Factor -
Article: Height, age at menarche and risk of hormone receptor positive and negative breast cancer: A cohort study.
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ABSTRACT: Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone-receptor defined malignancies. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of ER-PR- (n=990) and ER+PR+ (n=3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (HR: 1.14[95%CI 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years), showed an almost two-fold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. © 2012 Wiley Periodicals, Inc.International Journal of Cancer 10/2012; · 5.44 Impact Factor -
Article: Prospective Study on Physical Activity and Risk of In Situ Breast Cancer.
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ABSTRACT: BACKGROUND: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare. METHODS: The study included data from 283,827 women of the multinational EPIC-cohort study. Detailed information on different types of physical activity performed during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors were assessed at baseline. Adjusted hazard ratios (HR) for in situ breast cancer were estimated by Cox proportional hazards models. RESULTS: During a median follow-up period of 11.7 years, 1,059 incident breast carcinoma in situ were identified. In crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active and active participants with inactive study participants resulted in adjusted HRs of 0.99 (95%-CI 0.83-1.19), 0.99 (95%-CI 0.82-1.20), and 1.07 (95% CI 0.81-1.40), respectively (p-value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or BMI status. CONCLUSIONS: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. If not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis.Cancer Epidemiology Biomarkers & Prevention 10/2012; · 4.12 Impact Factor -
Article: Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort.
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ABSTRACT: Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use, and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analysed, only younger age at menarche (<12 vs 13 yrs) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR=1.44; 95% CI=0.99-2.10). CYP17A1 rs619824 was associated with HRT use (P-value=0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort. © 2012 Wiley Periodicals, Inc.International Journal of Cancer 09/2012; · 5.44 Impact Factor -
Article: Physical activity and risk of breast cancer overall and by hormone receptor status: The European prospective investigation into cancer and nutrition.
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ABSTRACT: Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.86-0.99, HR = 0.87, 95%-CI: 0.79-0.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.77-0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.64-0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER-/PR- tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.International Journal of Cancer 08/2012; · 5.44 Impact Factor -
Article: Determinants of age at menarche and time to menstrual cycle regularity in the French E3N cohort.
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ABSTRACT: Early menarche has been associated with a greater risk of several major chronic diseases. Although largely genetically determined, age at menarche also has been related to environmental and lifestyle factors. Using linear regression models, we explored simultaneously several pre- and postnatal factors as potential determinants of age at menarche and time to menstrual cycle regularity in 96,493 women participating, since 1990, in the French E3N prospective cohort. Younger age at recruitment, greater father's income index, urban birth place, greater birth length, and larger body silhouette during childhood were associated with an earlier age at menarche (from -1.3 to -4.6 months, P(trend) < .0001) whereas greater family size, food deprivation during childhood, and greater birth weight resulted in a delayed menarche (from +1.5 months to +5.3 months, P(trend) < .0001). Father's income index, urban birth place, and prematurity predicted a shorter time to menstrual cycle regularity (from -1.1 to -1.9 months, P(trend) < .04), whereas birth cohort, larger body silhouette at menarche, and childhood exposure to passive smoking were associated with a longer time to menstrual cycle regularity (from +1.1 months to +8.6 months, P(trend) < .006). Age at menarche and menstrual cycle regularity are significantly influenced by several individual, environmental and lifestyle factors.Annals of epidemiology 08/2012; 22(10):723-30. · 2.95 Impact Factor -
Article: Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.
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ABSTRACT: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.Breast cancer research: BCR 05/2012; 14(3):R76. · 5.24 Impact Factor -
Article: Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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ABSTRACT: ObjectiveTo evaluate the association between lifestyle and dietary factors and serum concentrations of androgens in middle-aged healthy men. MethodsWe conducted a cross-sectional analysis of the association of lifestyle factors with circulating concentrations of androstenedione (A-dione), 3-α-androstanediol glucuronide (A-diol-g), testosterone (T), SHBG (sex hormone-binding globulin), and free testosterone (FT) among 636 men in the European Prospective Investigation into Cancer and Nutrition. ResultsCompared with the youngest age group (40–49years), the oldest (70–79years) had a higher mean concentration of SHBG (by 44%) and lower mean concentrations of A-diol-g (by 29%) FT (19%). Men in the highest BMI group (≥29.83kg/m2) had a higher mean A-diol-g concentration (by 38%) and lower mean concentration of T (by 20%) SHBG (29%) compared with the lowest (<24.16kg/m2). Current smokers had higher mean concentrations of T (by 13%), SHBG (14%), and A-dione (15%) compared with never smokers. Physical activity and dietary factors were not associated with androgen concentrations, although men in the highest fifth of alcohol intake had higher mean concentrations of A-dione (by 9%), FT (11%) compared with the lowest. ConclusionOur results suggest that age, body weight, smoking, and alcohol intake are associated with circulating androgen concentrations in men.Cancer Causes and Control 04/2012; 20(6):811-821. · 2.88 Impact Factor -
Article: Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis.
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ABSTRACT: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% CI: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer.American Journal of Clinical Nutrition 03/2012; 95(5):1172-81. · 6.67 Impact Factor -
Article: Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.
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ABSTRACT: The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.PLoS ONE 01/2012; 7(7):e39821. · 4.09 Impact Factor -
Article: Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European Prospective Investigation into Cancer and Nutrition.
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ABSTRACT: Insulin-like growth factor-1 (IGF-I) is important in normal brain development but in the adult brain, IGF-I overexpression may be a risk factor for tumor development. We examined the association between circulating concentrations of IGF-I and IGFBP-3 in relation to risk of gliomas (74 low-grade, 206 high-grade gliomas), meningiomas (n = 174) and acoustic neuromas (n = 49) by using a case-control design nested in the European Prospective Investigation into Cancer and Nutrition. IGF-I and IGFBP-3 were measured by ELISAs.Conditional logistic regression was used to compute ORs and corresponding 95% CIs. The risk of low-grade gliomas was elevated with increased IGF-I (OR = 3.60, 95% CI: 1.11-11.7; top vs. bottom quartile) and decreased with elevated IGFBP-3 concentrations (OR = 0.28, 95% CI: 0.09-0.84) after mutual adjustment of these two factors; these results became nonsignificant after exclusion of the first year of follow-up. No association was observed for high-grade gliomas or meningiomas. Both high IGF-I and IGFBP-3 concentrations were associated with risk of acoustic neuromas (IGF-I: OR = 6.63, 95% CI: 2.27-19.4, top vs. bottom tertile; IGFBP-3: OR = 7.07, 95% CI: 2.32-21.6), even after excluding the first year of follow-up. High concentrations of IGF-I might be positively associated with risk of low-grade gliomas and acoustic neuromas, although we cannot exclude reverse causation, in particular for low-grade gliomas. Factors of the IGF axis might be involved in the etiology of some types of brain tumors.Cancer Epidemiology Biomarkers & Prevention 08/2011; 20(10):2174-82. · 4.12 Impact Factor -
Article: Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study.
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ABSTRACT: Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of hormone receptor [estrogen receptor (ER) and/or progesterone receptor (PR)] defined breast cancer. In a case-control study nested within the EPIC cohort (European Prospective Investigation into Cancer and Nutrition), estradiol, testosterone, and sex hormone-binding globulin levels were measured in prediagnostic serum samples from postmenopausal women not using hormone replacement therapy at blood donation. A total of 554 women who developed invasive breast cancer with information on receptor status were matched with 821 control subjects. Conditional logistic regression models estimated breast cancer risk with hormone concentrations according to hormone receptor status of the tumor. Sex steroid hormones were associated with risks of not only ER+PR+ breast cancer [estradiol OR for highest vs. lowest tertile = 2.91 (95% CI: 1.62-5.23), P(trend) = 0.002; testosterone OR = 2.27 (95% CI: 1.35-3.81), P(trend) = 0.002] but also of ER-PR- breast cancer [estradiol OR = 2.11 (95% CI: 1.00-4.46), P(trend) = 0.05; testosterone OR = 2.06 (95% CI: 0.95-4.46), P(trend) = 0.03], with associations appearing somewhat stronger in the receptor-positive disease. Serum androgens and estrogens are associated with risks of both hormone receptor-negative as well as receptor-positive breast tumors. Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors.Cancer Prevention Research 08/2011; 4(10):1626-35. · 4.91 Impact Factor -
Article: The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort.
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ABSTRACT: Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.International Journal of Cancer 06/2011; 130(10):2428-37. · 5.44 Impact Factor -
Article: Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition.
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ABSTRACT: The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.Cancer Causes and Control 06/2011; 22(8):1075-84. · 2.88 Impact Factor
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Institutions
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2012
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Université Paris-Sud 11
Paris, Ile-de-France, France
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2008–2012
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Deutsches Krebsforschungszentrum
- Division of Cancer Epidemiology
Heidelberg, Baden-Wuerttemberg, Germany -
University of Southern California
- Department of Preventive Medicine
Los Angeles, CA, USA
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2008–2011
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University of Oxford
- • Nuffield Department of Clinical Medicine
- • Division of Medical Sciences
Oxford, ENG, United Kingdom
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2009
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Deutsches Institut für Ernährungsforschung
- Department of Epidemiology
Potsdam, Brandenburg, Germany
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2005–2008
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International Agency for Research on Cancer
Lyon, Rhone-Alpes, France
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2007
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Cambridge University
Sydney, New South Wales, Australia
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