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


    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.


    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].


    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.


    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.

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    K01 CA160607/CA/NCI NIH HHS/United States
    CA77305/CA/NCI NIH HHS/United States
    R01 CA63446/CA/NCI NIH HHS/United States
    HHSN261201000036C/PHS HHS/United States
    U54 CA153511/CA/NCI NIH HHS/United States
    CA078682/CA/NCI NIH HHS/United States
    P30-AG15272/AG/NIA NIH HHS/United States
    P30 AG015272/AG/NIA NIH HHS/United States
    1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States
    R01 CA140002/CA/NCI NIH HHS/United States
    CA120120/CA/NCI NIH HHS/United States
    CA078552/CA/NCI NIH HHS/United States
    CA 160607/CA/NCI NIH HHS/United States
    N01-PC-67000/PC/NCI NIH HHS/United States
    CA14002/CA/NCI NIH HHS/United States
    CA078762/CA/NCI NIH HHS/United States
    R01 CA120120/CA/NCI NIH HHS/United States
    K24 CA169004/CA/NCI NIH HHS/United States
    CA63446/CA/NCI NIH HHS/United States
    CA078802/CA/NCI NIH HHS/United States
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