Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women

Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1731-8. doi: 10.1158/1055-9965.EPI-15-0392. Epub 2015 Sep 12.

Abstract

Background: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population.

Methods: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions.

Results: We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014].

Conclusions: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women.

Impact: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Breast Neoplasms / ethnology*
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / ethnology*
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Hispanic Americans / genetics*
  • Hispanic Americans / statistics & numerical data
  • Humans
  • Indians, North American / genetics
  • Life Style / ethnology
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors