The influence of single nucleotide polymorphisms on the association between dietary acrylamide intake and endometrial cancer risk

Sci Rep. 2016 Oct 7;6:34902. doi: 10.1038/srep34902.

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.

MeSH terms

  • Acrylamide / administration & dosage
  • Acrylamide / metabolism
  • Acrylamide / toxicity*
  • Aged
  • Carcinogens / administration & dosage
  • Carcinogens / metabolism
  • Carcinogens / toxicity
  • Cohort Studies
  • Cytochrome P-450 CYP2E1 / genetics
  • Diet / adverse effects*
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / etiology*
  • Endometrial Neoplasms / genetics*
  • Female
  • Gene Deletion
  • Genetic Association Studies
  • Glutathione Transferase / genetics
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors

Substances

  • Carcinogens
  • Acrylamide
  • Cytochrome P-450 CYP2E1
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1