20 july 2018

Alcohol drinking, ADH1B and ADH1C genotypes, and the risk of postmenopausal breast cancer by hormone receptor status: The Netherlands Cohort Study on Diet and Cancer

Alcohol has consistently been shown to increase breast cancer (BC) risk. This association may be modified by single nucleotide polymorphisms in alcohol dehydrogenase isoenzymes ADH1B and ADH1C. The Netherlands Cohort Study comprises 62 573 women, aged 55-69 years at baseline (1986). Follow-up for postmenopausal BC for 20.3 years was available. Genotyping of 6 tag SNPs in ADH1B and ADH1C, respectively, was performed on DNA from toenails. A case-cohort approach was used for analysis (complete data available for: nsubcohort= 1301; ncases= 1630). Cox regression models for postmenopausal BC were applied to determine marginal effects of alcohol intake and SNPs using a dominant genetic model, as well as multiplicative interaction of the two. Results were also obtained for subtypes by estrogen (ER) and progesterone receptor (PR) status. Multiple testing was adjusted for by applying the false discovery rate (FDR). Alcohol intake (categorical) increased the risk of postmenopausal BC (ptrend=0.031). Trends for ER and PR subgroups followed a similar pattern. Continuous modelling of alcohol resulted in a hazard rate ratio (HR) for overall postmenopausal BC of 1.09 (95% CI: 1.01 - 1.19) per 10g/d of alcohol. SNPs were not associated with BC risk. No effect modification of the alcohol-BC association by SNP genotype was seen after FDR-correction in overall BC and ER/PR subgroups. In conclusion, alcohol was shown to increase the risk of postmenopausal BC. This association was not significantly modified by common ADH1B and ADH1C SNPs, neither in overall BC nor in hormone receptor defined subtypes.

Additional Info

  • Authors

    Hahn M.; Simons C.C.J.M.; Weijenberg M.P.; van den Brandt P.A.
  • Issue

    Carcinogenesis
  • Published Date

    20 july 2018