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

About this Publication
Title
Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.
Pubmed ID
32359158 (View this publication on the PubMed website)
Digital Object Identifier
Publication
J Natl Cancer Inst. 2021 Mar 1; Volume 113 (Issue 3): Pages 329-337
Authors
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 LEB, Becher H, ...show more Beckmann MW, 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 PA, Figueroa J, Fritschi L, Gabrielson M, Gago-Dominguez M, Gao C, Gapstur SM, Gaudet MM, Giles GG, González-Neira A, Guénel P, Haeberle L, Haiman CA, Håkansson N, Hall P, Hamann U, Hatse S, Heyworth J, Holleczek B, Hoover RN, Hopper JL, Howell A, Hunter DJ, ABCTB Investigators, kConFab/AOCS Investigators, 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 PDP, Schmidt MK, Kraft P, Easton DF, Milne RL, García-Closas M, Chang-Claude J
Affiliations
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
  • Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
  • Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
  • Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.
  • Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Public Health Sciences and Cancer Research Institute, Queen's University, Kingston, ON, Canada.
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
...show more
  • Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
  • Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
  • Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.
  • Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
  • Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
  • Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
  • Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
  • School of Public Health, Curtin University, Perth, Western Australia, Australia.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
  • Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Laboratory of Experimental Oncology (LEO), Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
  • School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
  • Saarland Cancer Registry, Saarbrücken, Germany.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Division of Cancer Sciences, University of Manchester, Manchester, UK.
  • Division of Oncology, Departments of Epidemiology & Population Health and of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
  • VIB Center for Cancer Biology, VIB, Leuven, Belgium.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
  • General and Gastroenterology Surgery Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
  • Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria, Australia.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  • Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
  • Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Ireland, UK.
  • Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Human Genotyping-CEGEN Unit, Human Cancer Genetic Program, Spanish National Cancer Research Centre, Madrid, Spain.
  • Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
  • Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Department of Surgical Oncology, University Hospitals Leuven, Leuven, Belgium.
  • Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  • Population Oncology, BC Cancer, Vancouver, BC, Canada.
  • Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  • Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  • Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
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.

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