Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women. Wang, X., Kapoor, P. M., Auer, P. L., Dennis, J., Dunning, A. M., Wang, Q., Lush, M., Michailidou, K., Bolla, M. K., Aronson, K. J., Murphy, R. A., Brooks-Wilson, A., Lee, D. G., Cordina-Duverger, E., Guénel, P., Truong, T., Mulot, C., Teras, L. R., Patel, A. V., Dossus, L., Kaaks, R., Hoppe, R., Lo, W., Brüning, T., Hamann, U., Czene, K., Gabrielson, M., Hall, P., Eriksson, M., Jung, A., Becher, H., Couch, F. J., Larson, N. L., Olson, J. E., Ruddy, K. J., Giles, G. G., MacInnis, R. J., Southey, M. C., Le Marchand, L., Wilkens, L. R., Haiman, C. A., Olsson, H., Augustinsson, A., Krüger, U., Wagner, P., Scott, C., Winham, S. J., Vachon, C. M., Perou, C. M., Olshan, A. F., Troester, M. A., Hunter, D. J., Eliassen, H. A., Tamimi, R. M., Brantley, K., Andrulis, I. L., Figueroa, J., Chanock, S. J., Ahearn, T. U., García-Closas, M., Evans, G. D., Newman, W. G., van Veen, E. M., Howell, A., Wolk, A., Håkansson, N., Anton-Culver, H., Ziogas, A., Jones, M. E., Orr, N., Schoemaker, M. J., Swerdlow, A. J., Kitahara, C. M., Linet, M., Prentice, R. L., Easton, D. F., Milne, R. L., Kraft, P., Chang-Claude, J., & Lindström, S. Scientific Reports, 12(1):6199, April, 2022.
doi abstract bibtex

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values \textless 5 × 10-8 as genome-wide significant, and p-values \textless 1 × 10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values \textless 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10-7), which showed genome-wide significant interaction (p-value = 3.8 × 10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.

@article{wang_genome-wide_2022,
	title = {Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women},
	volume = {12},
	issn = {2045-2322},
	doi = {10.1038/s41598-022-10121-2},
	abstract = {Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values {\textless} 5 × 10-8 as genome-wide significant, and p-values {\textless} 1 × 10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values {\textless} 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10-7), which showed genome-wide significant interaction (p-value = 3.8 × 10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.},
	language = {eng},
	number = {1},
	journal = {Scientific Reports},
	author = {Wang, Xiaoliang and Kapoor, Pooja Middha and Auer, Paul L. and Dennis, Joe and Dunning, Alison M. and Wang, Qin and Lush, Michael and Michailidou, Kyriaki and Bolla, Manjeet K. and Aronson, Kristan J. and Murphy, Rachel A. and Brooks-Wilson, Angela and Lee, Derrick G. and Cordina-Duverger, Emilie and Guénel, Pascal and Truong, Thérèse and Mulot, Claire and Teras, Lauren R. and Patel, Alpa V. and Dossus, Laure and Kaaks, Rudolf and Hoppe, Reiner and Lo, Wing-Yee and Brüning, Thomas and Hamann, Ute and Czene, Kamila and Gabrielson, Marike and Hall, Per and Eriksson, Mikael and Jung, Audrey and Becher, Heiko and Couch, Fergus J. and Larson, Nicole L. and Olson, Janet E. and Ruddy, Kathryn J. and Giles, Graham G. and MacInnis, Robert J. and Southey, Melissa C. and Le Marchand, Loic and Wilkens, Lynne R. and Haiman, Christopher A. and Olsson, Håkan and Augustinsson, Annelie and Krüger, Ute and Wagner, Philippe and Scott, Christopher and Winham, Stacey J. and Vachon, Celine M. and Perou, Charles M. and Olshan, Andrew F. and Troester, Melissa A. and Hunter, David J. and Eliassen, Heather A. and Tamimi, Rulla M. and Brantley, Kristen and Andrulis, Irene L. and Figueroa, Jonine and Chanock, Stephen J. and Ahearn, Thomas U. and García-Closas, Montserrat and Evans, Gareth D. and Newman, William G. and van Veen, Elke M. and Howell, Anthony and Wolk, Alicja and Håkansson, Niclas and Anton-Culver, Hoda and Ziogas, Argyrios and Jones, Michael E. and Orr, Nick and Schoemaker, Minouk J. and Swerdlow, Anthony J. and Kitahara, Cari M. and Linet, Martha and Prentice, Ross L. and Easton, Douglas F. and Milne, Roger L. and Kraft, Peter and Chang-Claude, Jenny and Lindström, Sara},
	month = apr,
	year = {2022},
	pmid = {35418701},
	pmcid = {PMC9007944},
	keywords = {Breast, Breast Neoplasms, Estrogen Replacement Therapy, Female, Hormone Replacement Therapy, Humans, Male, Menopause, Risk Factors},
	pages = {6199},
}

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