Breast Cancer Research (Aug 2023)
A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- Pooja Middha,
- Xiaoliang Wang,
- Sabine Behrens,
- Manjeet K. Bolla,
- Qin Wang,
- Joe Dennis,
- Kyriaki Michailidou,
- Thomas U. Ahearn,
- Irene L. Andrulis,
- Hoda Anton-Culver,
- Volker Arndt,
- Kristan J. Aronson,
- Paul L. Auer,
- Annelie Augustinsson,
- Thaïs Baert,
- Laura E. Beane Freeman,
- Heiko Becher,
- Matthias W. Beckmann,
- Javier Benitez,
- Stig E. Bojesen,
- Hiltrud Brauch,
- Hermann Brenner,
- Angela Brooks-Wilson,
- Daniele Campa,
- Federico Canzian,
- Angel Carracedo,
- Jose E. Castelao,
- Stephen J. Chanock,
- Georgia Chenevix-Trench,
- CTS Consortium,
- Emilie Cordina-Duverger,
- Fergus J. Couch,
- Angela Cox,
- Simon S. Cross,
- Kamila Czene,
- Laure Dossus,
- Pierre-Antoine Dugué,
- A. Heather Eliassen,
- Mikael Eriksson,
- D. Gareth Evans,
- Peter A. Fasching,
- Jonine D. Figueroa,
- Olivia Fletcher,
- Henrik Flyger,
- Marike Gabrielson,
- Manuela Gago-Dominguez,
- Graham G. Giles,
- Anna González-Neira,
- Felix Grassmann,
- Anne Grundy,
- Pascal Guénel,
- Christopher A. Haiman,
- Niclas Håkansson,
- Per Hall,
- Ute Hamann,
- Susan E. Hankinson,
- Elaine F. Harkness,
- Bernd Holleczek,
- Reiner Hoppe,
- John L. Hopper,
- Richard S. Houlston,
- Anthony Howell,
- David J. Hunter,
- Christian Ingvar,
- ABCTB Investigators,
- kConFab Investigators,
- Karolin Isaksson,
- Helena Jernström,
- Esther M. John,
- Michael E. Jones,
- Rudolf Kaaks,
- Renske Keeman,
- Cari M. Kitahara,
- Yon-Dschun Ko,
- Stella Koutros,
- Allison W. Kurian,
- James V. Lacey,
- Diether Lambrechts,
- Nicole L. Larson,
- Susanna Larsson,
- Loic Le Marchand,
- Flavio Lejbkowicz,
- Shuai Li,
- Martha Linet,
- Jolanta Lissowska,
- Maria Elena Martinez,
- Tabea Maurer,
- Anna Marie Mulligan,
- Claire Mulot,
- Rachel A. Murphy,
- William G. Newman,
- Sune F. Nielsen,
- Børge G. Nordestgaard,
- Aaron Norman,
- Katie M. O’Brien,
- Janet E. Olson,
- Alpa V. Patel,
- Ross Prentice,
- Erika Rees-Punia,
- Gad Rennert,
- Valerie Rhenius,
- Kathryn J. Ruddy,
- Dale P. Sandler,
- Christopher G. Scott,
- Mitul Shah,
- Xiao-Ou Shu,
- Ann Smeets,
- Melissa C. Southey,
- Jennifer Stone,
- Rulla M. Tamimi,
- Jack A. Taylor,
- Lauren R. Teras,
- Katarzyna Tomczyk,
- Melissa A. Troester,
- Thérèse Truong,
- Celine M. Vachon,
- Sophia S. Wang,
- Clarice R. Weinberg,
- Hans Wildiers,
- Walter Willett,
- Stacey J. Winham,
- Alicja Wolk,
- Xiaohong R. Yang,
- M. Pilar Zamora,
- Wei Zheng,
- Argyrios Ziogas,
- Alison M. Dunning,
- Paul D. P. Pharoah,
- Montserrat García-Closas,
- Marjanka K. Schmidt,
- Peter Kraft,
- Roger L. Milne,
- Sara Lindström,
- Douglas F. Easton,
- Jenny Chang-Claude
Affiliations
- Pooja Middha
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Xiaoliang Wang
- Department of Epidemiology, University of Washington School of Public Health
- Sabine Behrens
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Manjeet K. Bolla
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Qin Wang
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Joe Dennis
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Kyriaki Michailidou
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Thomas U. Ahearn
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Irene L. Andrulis
- Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
- Hoda Anton-Culver
- Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine
- Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Kristan J. Aronson
- Department of Public Health Sciences, and Cancer Research Institute, Queen’s University
- Paul L. Auer
- Division of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin
- Annelie Augustinsson
- Oncology, Clinical Sciences in Lund, Lund University
- Thaïs Baert
- Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven
- Laura E. Beane Freeman
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Heiko Becher
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf
- Matthias W. Beckmann
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg
- Javier Benitez
- Human Genetics Group, Spanish National Cancer Research Centre (CNIO)
- Stig E. Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Hiltrud Brauch
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Angela Brooks-Wilson
- Canada’s Michael Smith Genome Sciences Centre, BC Cancer
- Daniele Campa
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
- Angel Carracedo
- Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS
- Jose E. Castelao
- Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS
- Stephen J. Chanock
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Georgia Chenevix-Trench
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute
- CTS Consortium
- Department of Computational and Quantitative Medicine, City of Hope
- Emilie Cordina-Duverger
- Team ‘Exposome and Heredity’, CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ
- Fergus J. Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic
- Angela Cox
- Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield
- Simon S. Cross
- Academic Unit of Pathology, Department of Neuroscience, University of Sheffield
- Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Laure Dossus
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO)
- Pierre-Antoine Dugué
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University
- A. Heather Eliassen
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
- Mikael Eriksson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- D. Gareth Evans
- Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, University of Manchester
- Peter A. Fasching
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg
- Jonine D. Figueroa
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Olivia Fletcher
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Henrik Flyger
- Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Marike Gabrielson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Manuela Gago-Dominguez
- Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS
- Graham G. Giles
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University
- Anna González-Neira
- Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)
- Felix Grassmann
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Anne Grundy
- Department of Public Health Sciences, Queen’s University
- Pascal Guénel
- Team ‘Exposome and Heredity’, CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ
- Christopher A. Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California
- Niclas Håkansson
- Institute of Environmental Medicine, Karolinska Institutet
- Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
- Susan E. Hankinson
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
- Elaine F. Harkness
- Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester
- Bernd Holleczek
- Saarland Cancer Registry
- Reiner Hoppe
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Richard S. Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Anthony Howell
- Division of Cancer Sciences, University of Manchester
- David J. Hunter
- Department of Epidemiology, Harvard T.H. Chan School of Public Health
- Christian Ingvar
- Surgery, Clinical Sciences in Lund, Lund University
- ABCTB Investigators
- Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney
- kConFab Investigators
- Research Department, Peter MacCallum Cancer Center
- Karolin Isaksson
- Department of Surgery, Kristianstad Hospital
- Helena Jernström
- Oncology, Clinical Sciences in Lund, Lund University
- Esther M. John
- Department of Epidemiology and Population Health, Stanford University School of Medicine
- Michael E. Jones
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Cari M. Kitahara
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Yon-Dschun Ko
- Department of Internal Medicine, Johanniter GmbH Bonn, Johanniter Krankenhaus
- Stella Koutros
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Allison W. Kurian
- Department of Epidemiology and Population Health, Stanford University School of Medicine
- James V. Lacey
- Department of Computational and Quantitative Medicine, City of Hope
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
- Nicole L. Larson
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic
- Susanna Larsson
- Institute of Environmental Medicine, Karolinska Institutet
- Loic Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center
- Flavio Lejbkowicz
- Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine
- Shuai Li
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Martha Linet
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Jolanta Lissowska
- Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Oncology Institute
- Maria Elena Martinez
- Moores Cancer Center and Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego
- Tabea Maurer
- Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf
- Anna Marie Mulligan
- Department of Laboratory Medicine and Pathobiology, University of Toronto
- Claire Mulot
- INSERM UMR-S1138. CRB EPIGENETEC, Université Paris Cité
- Rachel A. Murphy
- School of Population and Public Health, University of British Columbia
- William G. Newman
- Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, University of Manchester
- Sune F. Nielsen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Børge G. Nordestgaard
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Aaron Norman
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic
- Katie M. O’Brien
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH
- Janet E. Olson
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic
- Alpa V. Patel
- Department of Population Science, American Cancer Society
- Ross Prentice
- Cancer Prevention Program, Fred Hutchinson Cancer Research Center
- Erika Rees-Punia
- Department of Population Science, American Cancer Society
- Gad Rennert
- Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine
- Valerie Rhenius
- Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Kathryn J. Ruddy
- Department of Oncology, Mayo Clinic
- Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH
- Christopher G. Scott
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic
- Mitul Shah
- Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
- Ann Smeets
- Department of Surgical Oncology, University Hospitals Leuven
- Melissa C. Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University
- Jennifer Stone
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Rulla M. Tamimi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health
- Jack A. Taylor
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH
- Lauren R. Teras
- Department of Population Science, American Cancer Society
- Katarzyna Tomczyk
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Melissa A. Troester
- Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Thérèse Truong
- Team ‘Exposome and Heredity’, CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ
- Celine M. Vachon
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic
- Sophia S. Wang
- Department of Computational and Quantitative Medicine, City of Hope
- Clarice R. Weinberg
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH
- Hans Wildiers
- Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven
- Walter Willett
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
- Stacey J. Winham
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic
- Alicja Wolk
- Institute of Environmental Medicine, Karolinska Institutet
- Xiaohong R. Yang
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- M. Pilar Zamora
- Servicio de Oncología Médica, Hospital Universitario La Paz
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
- Argyrios Ziogas
- Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine
- Alison M. Dunning
- Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Paul D. P. Pharoah
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Montserrat García-Closas
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health
- Marjanka K. Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Peter Kraft
- Department of Epidemiology, Harvard T.H. Chan School of Public Health
- Roger L. Milne
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University
- Sara Lindström
- Department of Epidemiology, University of Washington School of Public Health
- Douglas F. Easton
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge
- Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- DOI
- https://doi.org/10.1186/s13058-023-01691-8
- Journal volume & issue
-
Vol. 25,
no. 1
pp. 1 – 13
Abstract
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.
Keywords
