Publications (7)43.97 Total impact
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Article: Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort.
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ABSTRACT: BACKGROUND:Studies in the United States and the United Kingdom have reported an increased risk of cholecystectomy among women exposed to menopausal hormone therapy, but with substantial heterogeneity between types of hormone treatments. We evaluated the risk of cholecystectomy associated with different regimens of menopausal hormone therapy in a large prospective cohort study. METHODS:Between 1992 and 2008, 70 928 menopausal women from the French E3N study cohort were sent questionnaires assessing their use of menopausal hormone therapy, medical history and lifestyle characteristics. The primary outcome was cholecystectomy. We analyzed the risk of cholecystectomy associated with use of menopausal hormone therapy using Cox proportional models, with age as time-scale. RESULTS:During follow-up, 45 984 (64.8%) of the participants were exposed to menopausal hormone therapy, and 2819 cholecystectomies were recorded. The use of menopausal hormone therapy was associated with an increased risk of cholecystectomy (adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.01-1.20) compared with women who were not exposed to menopausal hormone therapy. The association was restricted to unopposed oral estrogen therapy (adjusted HR 1.38, 95% CI 1.14-1.67). Over 5 years, about 1 cholecystectomy in excess would be expected in every 150 women using oral estrogen therapy without progestagens, compared with women not exposed to meno pausal hormone therapy. INTERPRETATION:The risk of cholecystectomy was increased among women exposed to oral estrogen meno pausal hormone therapy, especially oral regimens without a progestagen. Complicated gallstone disease should be added to the list of potential adverse events to be considered when balancing the benefits and risks associated with menopausal hormone therapy.Canadian Medical Association Journal 03/2013; · 8.22 Impact Factor -
Article: Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study.
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ABSTRACT: OBJECTIVE: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. DESIGN: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. RESULTS: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). CONCLUSIONS: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.Gut 09/2012; · 10.11 Impact Factor -
Article: Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort.
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ABSTRACT: Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P(trend) = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P(trend) = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P(trend) = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P(trend) = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. ©2012 AACR.Cancer Research 08/2012; 72(20):5328-5337. · 7.86 Impact Factor -
Article: Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.
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ABSTRACT: Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, ≥ 25 kg/m(2) ) with magnesium (HR(per 100 mg/day increase) = 0.79, 95% CI = 0.63-1.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR (per 1 mg/day increase) = 1.38, 95% CI = 1.10-1.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.22-5.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.International Journal of Cancer 03/2012; 131(7):E1134-47. · 5.44 Impact Factor -
Article: Prediagnostic 25-hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in western European ppulations.
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ABSTRACT: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown. The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated. There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (P(trend) = 0.04) and overall mortality (P(trend) = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50-0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50-0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (P(interaction) = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival. High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC. Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients.Cancer Epidemiology Biomarkers & Prevention 03/2012; 21(4):582-93. · 4.12 Impact Factor -
Article: The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort.
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ABSTRACT: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.Cancer Epidemiology Biomarkers & Prevention 02/2012; 21(4):619-28. · 4.12 Impact Factor -
Article: Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC).
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ABSTRACT: Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.PLoS ONE 01/2012; 7(6):e39361. · 4.09 Impact Factor