Journal
SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-10121-2
Keywords
-
Categories
Funding
- Cancer Research UK [C1287/A16563, C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565]
- European Union's Horizon 2020 Research and Innovation Programme [634935, 633784]
- European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]
- NIH [U19 CA148065, CA192393, CA116167, CA176785, CA116201, CA63464, CA54281, CA098758, CA132839, CA164973, P01 CA87969, UM1 CA186107, UM1 CA176726, CA58860, CA92044]
- Cancer UK [C1287/A16563]
- Government of Canada through Genome Canada
- Canadian Institutes of Health Research [GPH-129344]
- Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec
- Ministere de l'Economie, Science et Innovation du Quebec [PSRSIIRI-701]
- Quebec Breast Cancer Foundation
- European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]
- Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]
- Department of Defense [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR)
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- Canadian Cancer Society [313404]
- Canadian Institutes of Health Research
- Fondation de France, Institut National du Cancer (INCa)
- Ligue Nationale contre le Cancer
- Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES)
- Agence Nationale de la Recherche (ANR)
- American Cancer Society
- International Agency for Research on Cancer (IARC)
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer (France)
- Institut Gustave Roussy (France)
- Mutuelle Generale de l'Education Nationale (France)
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- German Cancer Aid (Germany)
- German Cancer Research Center (DKFZ) (Germany)
- German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)
- Federal Ministry of Education and Research (BMBF) (Germany)
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy (Italy)
- Compagnia di SanPaolo (Italy)
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands)
- Netherlands Cancer Registry (NKR) (The Netherlands)
- LK Research Funds (The Netherlands)
- Dutch Prevention Funds (The Netherlands)
- Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands (The Netherlands)
- Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain)
- Catalan Institute of Oncology-ICO (Spain)
- Regional Government of Andalucia (Spain)
- Regional Government of Asturias (Spain)
- Regional Government of Basque Country (Spain)
- Regional Government of Murcia (Spain)
- Regional Government of Navarra (Spain)
- Swedish Cancer Society (Sweden)
- Swedish Research Council (Sweden)
- County Council of Skane (Sweden)
- County Council Vasterbotten (Sweden)
- Cancer Research UK (United Kingdom) [14136, C8221/A29017]
- Medical Research Council (United Kingdom) [1000143, MR/M012190/1]
- Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]
- Robert Bosch Foundation, Stuttgart
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance
- Institute of the Ruhr University Bochum (IPA), Bochum
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany
- Marit and Hans Rausings Initiative Against Breast Cancer
- Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828]
- Hamburg Cancer Society
- German Cancer Research Center (DKFZ)
- VicHealth
- Cancer Council Victoria
- Australian National Health and Medical Research Council [209057, 396414, 1074383]
- Swedish Cancer Society
- Swedish Research Council
- Berta Kamprad Foundation
- Komen Foundation
- National Cancer Institute [P50 CA058223, U54 CA156733, U01 CA179715]
- North Carolina University Cancer Research Fund
- Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA
- Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics
- Intramural Research Program of the Division of Cancer Epidemiology and Genetics
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health
- NIHR [PGfAR 0707-10031]
- Agency for Science, Technology and Research of Singapore (A*STAR)
- US National Institute of Health (NIH)
- Susan G. Komen Breast Cancer Foundation
- Swedish Cancer Foundation
- Swedish Research Council [VR 2017-00644]
- Lon V Smith Foundation [LVS39420]
- Breast Cancer Now
- Institute of Cancer Research (ICR), London
- NHS
- National Heart, Lung, and Blood Institute
- US National Institutes of Health
- US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- NCI [U19 CA148065-01]
- [ERC-2011-294576]
Ask authors/readers for more resources
This study found limited evidence that common genetic variants modify the effect of menopausal hormone therapy (MHT) on breast cancer risk.
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 x 10(-8) as genome-wide significant, and p-values < 1 x 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 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available