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

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC9007944 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Wang Xiaoliang X Kapoor Pooja Middha PM Auer Paul L PL Dennis Joe J Dunning Alison M AM Wang Qin Q Lush Michael M Michailidou Kyriaki K Bolla Manjeet K MK Aronson Kristan J KJ Murphy Rachel A RA Brooks-Wilson Angela A Lee Derrick G DG Cordina-Duverger Emilie E Guénel Pascal P Truong Thérèse T Mulot Claire C Teras Lauren R LR Patel Alpa V AV Dossus Laure L Kaaks Rudolf R Hoppe Reiner R Lo Wing-Yee WY Brüning Thomas T Hamann Ute U Czene Kamila K Gabrielson Marike M Hall Per P Eriksson Mikael M Jung Audrey A Becher Heiko H Couch Fergus J FJ Larson Nicole L NL Olson Janet E JE Ruddy Kathryn J KJ Giles Graham G GG MacInnis Robert J RJ Southey Melissa C MC Le Marchand Loic L Wilkens Lynne R LR Haiman Christopher A CA Olsson Håkan H Augustinsson Annelie A Krüger Ute U Wagner Philippe P Scott Christopher C Winham Stacey J SJ Vachon Celine M CM Perou Charles M CM Olshan Andrew F AF Troester Melissa A MA Hunter David J DJ Eliassen Heather A HA Tamimi Rulla M RM Brantley Kristen K Andrulis Irene L IL Figueroa Jonine J Chanock Stephen J SJ Ahearn Thomas U TU García-Closas Montserrat M Evans Gareth D GD Newman William G WG van Veen Elke M EM Howell Anthony A Wolk Alicja A Håkansson Niclas N Anton-Culver Hoda H Ziogas Argyrios A Jones Michael E ME Orr Nick N Schoemaker Minouk J MJ Swerdlow Anthony J AJ Kitahara Cari M CM Linet Martha M Prentice Ross L RL Easton Douglas F DF Milne Roger L RL Kraft Peter P Chang-Claude Jenny J Lindström Sara S

Scientific reports 20220413 1

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 multiplicat ...[more]

PMID: 35418701

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Project description:We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy.This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ?2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy.Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (?51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (?51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant.Our findings suggest that associations of mammographic density with breast cancer risk differ by tumor aggressiveness. While there was no strong evidence that these associations differed by menopausal status or hormone therapy, they did appear more prominent among current estrogen+progesterone users.

Dataset Information

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

Publications

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

Similar Datasets

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