Interactions between dietary acrylamide intake and genes for ovarian cancer risk

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 Mass-ARRAY 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. This study was funded by the Dutch Cancer Society (KWF), grant number: UM 2011-5123. Janneke Hogervorst is a postdoctoral research fellow from the Research Foundation-Flanders (FWO), No. 12J9516N. The authors thank the study participants, the Netherlands Cancer Registry, the Dutch Pathology Registry, and the Biobank of the Maastricht University Medical Center. We thank Dr. Sandra Bausch as initiator of the NLCS study, together with Prof. Piet van den Brandt. We also thank Sacha van de Crommert, Jolanda Nelissen, Conny de Zwart, Ellen Dutman, Henny Brants, and Annemie Pisters for their assistance with data entry or data management, Harry van Montfort for programming assistance, and Stijn Lumeij, Kristien Lemmens, Joy Goessens, and Leonie Jonkers for technical assistance with DNA isolation and genotyping.