Interaction between common breast cancer susceptibility variants, genetic ancestry, and non-genetic risk factors in Hispanic women
Menée aux Etats-Unis à partir de données portant sur 2 107 patientes hispaniques atteintes d'un cancer du sein et sur 2 587 témoins, cette étude évalue l'association entre 10 polymorphismes à simple nucléotide précédemment identifiés dans des études d'association sur le génome entier en population non différenciée, des facteurs de risque de cancer non génétiques (mode de vie, facteurs hormonaux) et des ancêtres hispaniques
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 single nucleotide polymorphisms (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 odds ratio (OR): 0.94 (95% confidence interval 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, P-interaction 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, P-interaction 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 non-genetic risk factors and their contribution to breast cancer risk.