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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

ABSTRACT: Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

SUBMITTER: Agudo A

PROVIDER: S-EPMC3670256 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Agudo Antonio A Bonet Catalina C Sala Núria N Muñoz Xavier X Aranda Núria N Fonseca-Nunes Ana A Clavel-Chapelon Françoise F Boutron-Ruault Marie Christine MC Vineis Paolo P Panico Salvatore S Palli Domenico D Tumino Rosario R Grioni Sara S Quirós J Ramón JR Molina Esther E Navarro Carmen C Barricarte Aurelio A Chamosa Saioa S Allen Naomi E NE Khaw Kay-Tee KT Bueno-de-Mesquita H Bas HB Siersema Peter D PD Numans Mattijs E ME Trichopoulou Antonia A Lagiou Pagona P Trichopoulos Dimitrios D Kaaks Rudof R Canzian Federico F Boeing Heiner H Meidtner Karina K Johansson Mattias M Sund Malin M Manjer Jonas J Overvad Kim K Tjonneland Anne A Lund Eiliv E Weiderpass Elisabete E Jenab Mazda M Fedirko Veronika V Offerhaus G Johan A GJ Riboli Elio E González Carlos A CA Jakszyn Paula P

Carcinogenesis 20130206 6

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analys ...[more]

PMID: 23389292

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Project description:BackgroundProspective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents.Materials and methodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for relevant confounding variables.ResultsDuring the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98). Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82-0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02) in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99); this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99), with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81-1.24).ConclusionsOur results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.

Project description:BACKGROUND:The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. OBJECTIVE:We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk. DESIGN:The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa. RESULTS:Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake. CONCLUSIONS:Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results.

Dataset Information

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Publications

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

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