Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk

Kapoor PM, Mavaddat N, Choudhury PP, Wilcox AN, Lindström S, Behrens S, Michailidou K, Dennis J, Bolla MK, Wang Q, Jung A, Abu-Ful Z, Ahearn T, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Freeman LE, Becher H, Beckmann M, Beeghly-Fadiel A, Benitez J, Bernstein L, Bojesen SE, Brauch H, Brenner H, Brüning T, Cai Q, Campa D, Canzian F, Carracedo A, Carter BD, Castelao JE, Chanock SJ, Chatterjee N, Chenevix-Trench G, Clarke CL, Couch FJ, Cox A, Cross SS, Czene K, Dai JY, Earp HS, Ekici AB, Eliassen AH, Eriksson M, Evans DG, Fasching P, Figueroa J, Fritschi L, Gabrielson M, Gago-Dominguez M, Gao C, Gapstur SM, Gaudet MM, Giles GG, González-Neira A, Guénel P, Häberle L, Haiman CA, Håkansson N, Hall P, Hamann U, Hatse S, Heyworth J, Holleczek B, Hoover RN, Hopper JL, Howell A, Hunter DJ, John EM, Jones ME, Kaaks R, Keeman R, Kitahara CM, Ko YD, Koutros S, Kurian AW, Lambrechts D, Le Marchand L, Lee E, Lejbkowicz F, Linet M, Lissowska J, Llaneza A, MacInnis RJ, Martinez ME, Maurer T, McLean C, Neuhausen SL, Newman WG, Norman A, O'Brien KM, Olshan AF, Olson JE, Olsson H, Orr N, Perou CM, Pita G, Polley EC, Prentice RL, Rennert G, Rennert HS, Ruddy KJ, Sandler DP, Saunders C, Schoemaker MJ, Schöttker B, Schumacher F, Scott C, Scott RJ, Shu XO, Smeets A, Southey MC, Spinelli JJ, Stone J, Swerdlow AJ, Tamimi RM, Taylor JA, Troester MA, Vachon CM, van Veen EM, Wang X, Weinberg CR, Weltens C, Willett W, Winham SJ, Wolk A, Yang XR, Zheng W, Ziogas A, Dunning AM, Pharoah PD, Schmidt MK, Kraft P, Easton DF, Milne RL, García-Closas M, Chang-Claude J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 113

Pages Range: 329-337

Journal Issue: 3

DOI: 10.1093/jnci/djaa056

Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Authors with CRIS profile

Involved external institutions

Mayo Clinic United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Stanford Cancer Institute United States (USA) (US) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) The Institute of Cancer Research (ICR) United Kingdom (GB) Melbourne School of Population and Global Health Australia (AU) Case Western Reserve University United States (USA) (US) University of Cambridge United Kingdom (GB) Technion - Israel Institute of Technology Israel (IL) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Fred Hutchinson Cancer Research Center Canada (CA) University of California Irvine United States (USA) (US) Vanderbilt University Medical Center United States (USA) (US) Monash University Australia (AU) Queen's University United Kingdom (GB) Antoni van Leeuwenhoek Netherlands (NL) Karolinska Institute Sweden (SE) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) University of Hawaiʻi at Mānoa United States (USA) (US) Queen's University Canada (CA) Mount Sinai Hospital (MSH) Canada (CA) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) University of Sydney (USYD) Australia (AU) Moores Cancer Center United States (USA) (US) Herlev Hospital Denmark (DK) City of Hope Medical Center United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) American Cancer Society United States (USA) (US) University of Sheffield United Kingdom (GB) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Johanniter GmbH Germany (DE) University of Manchester United Kingdom (GB) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Keck School of Medicine of USC United States (USA) (US) Ruhr-Universität Bochum (RUB) Germany (DE) The Alfred Hospital Australia (AU) Cancer Council Victoria Australia (AU) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University of Washington United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Harvard T.H. Chan School of Public Health United States (USA) (US) Curtin University Australia (AU) Central University Hospital of Asturias Spain (ES) University of North Carolina at Chapel Hill United States (USA) (US) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Lund University / Lunds universitet Sweden (SE) Instituto de Investigación Sanitaria Galicia Sur Spain (ES) University of Western Australia (UWA) Australia (AU) Population Oncology Canada (CA) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE)

How to cite

APA:

Kapoor, P.M., Mavaddat, N., Choudhury, P.P., Wilcox, A.N., Lindström, S., Behrens, S.,... Chang-Claude, J. (2021). Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk. Journal of the National Cancer Institute, 113(3), 329-337. https://doi.org/10.1093/jnci/djaa056

MLA:

Kapoor, Pooja Middha, et al. "Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk." Journal of the National Cancer Institute 113.3 (2021): 329-337.

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