title: Interactions between dietary acrylamide intake and genes for ovarian cancer risk.
abstract: Some epidemiological studies observed a positive association between dietary acrylamide intake and ovarian cancer risk but the causality needs to be substantiated. By analyzing gene-acrylamide interactions for ovarian cancer risk for the first time, we aimed to contribute to this. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline in 1986, a random subcohort of 2589 women was sampled from the total cohort for a case cohort analysis approach. Dietary acrylamide intake of subcohort members and ovarian cancer cases (n = 252, based on 20.3 years of follow-up) was assessed with a food frequency questionnaire. We selected single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism and in genes involved in the possible mechanisms of acrylamide-induced carcinogenesis (effects on sex steroid systems, oxidative stress and DNA damage). Genotyping was done on DNA from toenails through Agena's MassARRAY iPLEX platform. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions between acrylamide and gene variants after adjustment for multiple testing. However, there were several nominally statistically significant interactions between acrylamide intake and SNPs in the HSD3B1/B2 gene cluster: (rs4659175 (p interaction = 0.04), rs10923823 (p interaction = 0.06) and its proxy rs7546652 (p interaction = 0.05), rs1047303 (p interaction = 0.005), and rs6428830 (p interaction = 0.05). Although in need of confirmation, results of this study suggest that acrylamide may cause ovarian cancer through effects on sex hormones.
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium. jgf.hogervorst@maastrichtuniversity.nl.|Department of Epidemiology, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands. jgf.hogervorst@maastrichtuniversity.nl.
authors.forename: Janneke G F
authors.identifier: 0000-0003-1795-0128
authors.initials: JGF
authors.lastname: Hogervorst
authors.affiliation: Department of Epidemiology, School for Oncology and 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: RWL
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 and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
mesh_terms: D020106:Acrylamide / Q000378:metabolism* / Q000633:toxicity*; D000328:Adult; D000368:Aged; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011795:Surveys and Questionnaires
chemical_list: D020106:Acrylamide
keywords: Dietary acrylamide; Ovarian cancer; Prospective cohort; Single nucleotide polymorphism