Faculty Collaboration Database

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women. Sci Rep 2022 Apr 13;12(1):6199

Date

04/15/2022

Pubmed ID

35418701

Pubmed Central ID

PMC9007944

DOI

10.1038/s41598-022-10121-2

Scopus ID

2-s2.0-85128281436 (requires institutional sign-in at Scopus site)   2 Citations

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 < 5 × 10^-8 as genome-wide significant, and p-values < 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 < 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.

Author List

Wang X, Kapoor PM, Auer PL, Dennis J, Dunning AM, Wang Q, Lush M, Michailidou K, Bolla MK, Aronson KJ, Murphy RA, Brooks-Wilson A, Lee DG, Cordina-Duverger E, Guénel P, Truong T, Mulot C, Teras LR, Patel AV, Dossus L, Kaaks R, Hoppe R, Lo WY, Brüning T, Hamann U, Czene K, Gabrielson M, Hall P, Eriksson M, Jung A, Becher H, Couch FJ, Larson NL, Olson JE, Ruddy KJ, Giles GG, MacInnis RJ, Southey MC, Le Marchand L, Wilkens LR, Haiman CA, Olsson H, Augustinsson A, Krüger U, Wagner P, Scott C, Winham SJ, Vachon CM, Perou CM, Olshan AF, Troester MA, Hunter DJ, Eliassen HA, Tamimi RM, Brantley K, Andrulis IL, Figueroa J, Chanock SJ, Ahearn TU, García-Closas M, Evans GD, Newman WG, van Veen EM, Howell A, Wolk A, Håkansson N, Anton-Culver H, Ziogas A, Jones ME, Orr N, Schoemaker MJ, Swerdlow AJ, Kitahara CM, Linet M, Prentice RL, Easton DF, Milne RL, Kraft P, Chang-Claude J, Lindström S

Author

Paul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Breast
Breast Neoplasms
Estrogen Replacement Therapy
Female
Hormone Replacement Therapy
Humans
Male
Menopause
Risk Factors