Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 155, Issue 3, Pages 531-540Publisher
SPRINGER
DOI: 10.1007/s10549-016-3681-7
Keywords
Breast cancer; Menopausal hormone therapy; Genetic variation
Categories
Funding
- US National Institutes of Health
- National Cancer Institute [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]
- Intramural Research Program of National Institutes of Health
- National Cancer Institute, Division of Cancer Epidemiology and Genetics
- American Cancer Society
- Nurses' Health Study [UM1 186107, R01 CA49449]
- Nurses' Health Study II [UM1 176726, R01 CA67262]
- Women's Health Study [CA047988, HL043851, HL080467]
- National Heart, Lung, and Blood Institute, National Institutes of Health
- U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN2682011000 04C, HHSN271201100004C]
- Cancer Research UK [C570/A11691, C8221/A19170]
- [U01 CA164973]
- Cancer Research UK [16491, 14136] Funding Source: researchfish
- Medical Research Council [G0401527, G1000143] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114] Funding Source: researchfish
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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 x 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 x 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.
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