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Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium

  • Epidemiology
  • Published:
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Abstract

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.

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Acknowledgments

This work was supported, in part, by the US National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233-07 to D.J.H., U01-CA98710-06 to M.J.T., U01-CA98216-06 to E.R. and R.K., and U01-CA98758-07 to B.E.H.) and Intramural Research Program of National Institutes of Health and National Cancer Institute, Division of Cancer Epidemiology and Genetics. The American Cancer Society provided funds to Drs. Gaudet and Gapstur as well as for the creation, maintenance, and updating of the Cancer Prevention Study II (CPS-II) cohort. The Nurses’ Health Study (UM1 186107, R01 CA49449), the Nurses’ Health Study II (UM1 176726, R01 CA67262), and the Women’s Health Study (CA047988, HL043851 and HL080467) are supported by grants from the National Institutes of Health. The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.” The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. Ruth C Travis was supported by Cancer Research UK grants (C570/A11691 and C8221/A19170). The Multiethnic Cohort was supported by grant U01 CA164973.

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Mia M. Gaudet and Myrto Barrdahl have contributed equally to this work.

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Gaudet, M.M., Barrdahl, M., Lindström, S. et al. Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium. Breast Cancer Res Treat 155, 531–540 (2016). https://doi.org/10.1007/s10549-016-3681-7

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