A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Middha P, Wang X, Behrens S, Bolla MK, Wang Q, Dennis J, Michailidou K, Ahearn TU, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Augustinsson A, Baert T, Freeman LE, Becher H, Beckmann M, Benitez J, Bojesen SE, Brauch H, Brenner H, Brooks-Wilson A, Campa D, Canzian F, Carracedo A, Castelao JE, Chanock SJ, Chenevix-Trench G, Cordina-Duverger E, Couch FJ, Cox A, Cross SS, Czene K, Dossus L, Dugué PA, Eliassen AH, Eriksson M, Evans DG, Fasching P, Figueroa JD, Fletcher O, Flyger H, Gabrielson M, Gago-Dominguez M, Giles GG, González-Neira A, Grassmann F, Grundy A, Guénel P, Haiman CA, Håkansson N, Hall P, Hamann U, Hankinson SE, Harkness EF, Holleczek B, Hoppe R, Hopper JL, Houlston RS, Howell A, Hunter DJ, Ingvar C, Isaksson K, Jernström H, John EM, Jones ME, Kaaks R, Keeman R, Kitahara CM, Ko YD, Koutros S, Kurian AW, Lacey JV, Lambrechts D, Larson NL, Larsson S, Le Marchand L, Lejbkowicz F, Li S, Linet M, Lissowska J, Martinez ME, Maurer T, Mulligan AM, Mulot C, Murphy RA, Newman WG, Nielsen SF, Nordestgaard BG, Norman A, O'Brien KM, Olson JE, Patel AV, Prentice R, Rees-Punia E, Rennert G, Rhenius V, Ruddy KJ, Sandler DP, Scott CG, Shah M, Shu XO, Smeets A, Southey MC, Stone J, Tamimi RM, Taylor JA, Teras LR, Tomczyk K, Troester MA, Truong T, Vachon CM, Wang SS, Weinberg CR, Wildiers H, Willett W, Winham SJ, Wolk A, Yang XR, Zamora MP, Zheng W, Ziogas A, Dunning AM, Pharoah PD, García-Closas M, Schmidt MK, Kraft P, Milne RL, Lindström S, Easton DF, Chang-Claude J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 25

Pages Range: 93-

Journal Issue: 1

DOI: 10.1186/s13058-023-01691-8

Abstract

BACKGROUND: Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. METHODS: Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. RESULTS: Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). CONCLUSIONS: Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

University of Cambridge United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) University of California Irvine United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Queen's University Canada (CA) Medical College of Wisconsin (MCW) United States (USA) (US) Copenhagen University Hospital Denmark (DK) Mayo Clinic United States (USA) (US) Karolinska Institute Sweden (SE) International Agency for Research on Cancer (IARC) France (FR) American Cancer Society United States (USA) (US) Clalit Health Services Israel (IL) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Melbourne School of Population and Global Health Australia (AU) The Institute of Cancer Research (ICR) United Kingdom (GB) University of Washington United States (USA) (US) Lund University / Lunds universitet Sweden (SE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie Germany (DE) Canada's Michael Smith Genome Sciences Centre Canada (CA) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Instituto de Investigación Sanitaria Galicia Sur Spain (ES) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) University of Sheffield United Kingdom (GB) Monash University Australia (AU) Brigham and Women's Hospital (BWH) United States (USA) (US) University of Manchester United Kingdom (GB) Breast Cancer Now Toby Robins Research Centre United Kingdom (GB) Keck School of Medicine of USC United States (USA) (US) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Harvard T.H. Chan School of Public Health United States (USA) (US) Centralsjukhuset Kristianstad (CSK) Sweden (SE) Stanford University United States (USA) (US) Netherlands Cancer Institute (NKI) Netherlands (NL) Johanniter GmbH Germany (DE) City of Hope Medical Center United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) University of California, San Diego United States (USA) (US) University of Toronto Canada (CA) University of British Columbia Canada (CA) Fred Hutchinson Cancer Research Center Canada (CA) Vanderbilt University Medical Center United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Hospital Universitario La Paz Spain (ES)

How to cite

APA:

Middha, P., Wang, X., Behrens, S., Bolla, M.K., Wang, Q., Dennis, J.,... Chang-Claude, J. (2023). A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry. Breast Cancer Research, 25(1), 93-. https://doi.org/10.1186/s13058-023-01691-8

MLA:

Middha, Pooja, et al. "A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry." Breast Cancer Research 25.1 (2023): 93-.

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