title: The influence of single nucleotide polymorphisms on the association between dietary acrylamide intake and endometrial cancer risk.
abstract: It is unclear whether the association between dietary acrylamide intake and endometrial cancer risk as observed in some epidemiological studies reflects a causal relationship. We aimed at clarifying the causality by analyzing acrylamide-gene interactions for endometrial cancer risk. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was selected for a case cohort analysis approach. Acrylamide intake of subcohort members and endometrial cancer cases (n = 315) was assessed with a food frequency questionnaire. Single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair were assessed through a MassARRAY iPLEX Platform. Interaction between acrylamide and SNPs was assessed with Cox proportional hazards analysis, based on 11.3 years of follow-up. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions after adjustment for multiple testing. However, there were nominally statistically significant interactions for SNPs in acrylamide-metabolizing enzymes: CYP2E1 (rs915906 and rs2480258) and the deletions of GSTM1 and GSTT1. Although in need of confirmation, the interactions between acrylamide intake and CYP2E1 SNPs contribute to the evidence for a causal relationship between acrylamide and endometrial cancer risk.
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.|Department of Epidemiology, School for Oncology &Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands.
authors.forename: Janneke G F
authors.initials: JG
authors.lastname: Hogervorst
authors.affiliation: Department of Epidemiology, School for Oncology &Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands.
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.affiliation: Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.affiliation: Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: Frederik-Jan
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: Department of Epidemiology, School for Oncology &Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
mesh_terms: D020106:Acrylamide / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000368:Aged; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D015331:Cohort Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004032:Diet / Q000009:adverse effects*; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D020106:Acrylamide; D002273:Carcinogens; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1