Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.

Original publication

DOI

10.1007/s10549-016-3681-7

Type

Journal article

Journal

Breast Cancer Res Treat

Publication Date

02/2016

Volume

155

Pages

531 - 540

Keywords

Breast cancer, Genetic variation, Menopausal hormone therapy, Adult, Aged, Breast Neoplasms, Cohort Studies, Disease Susceptibility, Female, Genetic Association Studies, Genotype, Hormone Replacement Therapy, Humans, Male, Menopause, Middle Aged, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Factors