Breast Cancer Research (Jun 2023)
Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium
- Karin Kast,
- Esther M. John,
- John L. Hopper,
- Nadine Andrieu,
- Catherine Noguès,
- Emmanuelle Mouret-Fourme,
- Christine Lasset,
- Jean-Pierre Fricker,
- Pascaline Berthet,
- Véronique Mari,
- Lucie Salle,
- Marjanka K. Schmidt,
- Margreet G. E. M. Ausems,
- Encarnacion B. Gomez Garcia,
- Irma van de Beek,
- Marijke R. Wevers,
- D. Gareth Evans,
- Marc Tischkowitz,
- Fiona Lalloo,
- Jackie Cook,
- Louise Izatt,
- Vishakha Tripathi,
- Katie Snape,
- Hannah Musgrave,
- Saba Sharif,
- Jennie Murray,
- EMBRACE Collaborators,
- Sarah V. Colonna,
- Irene L. Andrulis,
- Mary B. Daly,
- Melissa C. Southey,
- Miguel de la Hoya,
- Ana Osorio,
- Lenka Foretova,
- Dita Berkova,
- Anne-Marie Gerdes,
- Edith Olah,
- Anna Jakubowska,
- Christian F. Singer,
- Yen Tan,
- Annelie Augustinsson,
- Johanna Rantala,
- Jacques Simard,
- Rita K. Schmutzler,
- Roger L. Milne,
- Kelly-Anne Phillips,
- Mary Beth Terry,
- David Goldgar,
- Flora E. van Leeuwen,
- Thea M. Mooij,
- Antonis C. Antoniou,
- Douglas F. Easton,
- Matti A. Rookus,
- Christoph Engel
Affiliations
- Karin Kast
- Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
- Esther M. John
- Department of Epidemiology & Population Health and of Medicine (Oncology), Stanford University School of Medicine
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Nadine Andrieu
- INSERM U900
- Catherine Noguès
- Aix Marseille Université, INSERM, IRD, SESSTIM
- Emmanuelle Mouret-Fourme
- Institut Curie
- Christine Lasset
- Centre Léon Bérard
- Jean-Pierre Fricker
- CRLCC Paul Strauss
- Pascaline Berthet
- Centre François Baclesse
- Véronique Mari
- Centre Antoine Lacassagne
- Lucie Salle
- Oncogénétique Poitou-Charentes
- Marjanka K. Schmidt
- Division of Molecular Pathology, Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital
- Margreet G. E. M. Ausems
- Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht
- Encarnacion B. Gomez Garcia
- Department of Clinical Genetics, Maastricht University Medical Center
- Irma van de Beek
- Department of Human Genetics, Amsterdam UMC, University of Amsterdam
- Marijke R. Wevers
- Department of Clinical Genetics, Radboud University Medical Center
- D. Gareth Evans
- The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust
- Marc Tischkowitz
- Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge
- Fiona Lalloo
- Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust
- Jackie Cook
- Sheffield Clinical Genetics Service, Sheffield Children’s Hospital
- Louise Izatt
- Department of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust
- Vishakha Tripathi
- Clinical Genetics Service, Guy’s and St Thomas’ NHS Foundation Trust
- Katie Snape
- Department of Clinical Genetics, St George’s University Hospitals NHS Foundation Trust
- Hannah Musgrave
- Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust
- Saba Sharif
- West Midlands Regional Genetics Service, Birmingham Women’s Hospital Healthcare NHS Trust
- Jennie Murray
- South East of Scotland Regional Genetics Service, Western General Hospital
- EMBRACE Collaborators
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Sarah V. Colonna
- Department of Medicine and Huntsman Cancer Institute, University of Utah Health
- Irene L. Andrulis
- Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
- Mary B. Daly
- Department of Clinical Genetics, Fox Chase Cancer Center
- Melissa C. Southey
- Precision Medicine, School of Clinical Sciences at, Monash Health Monash University
- Miguel de la Hoya
- Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
- Ana Osorio
- Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and Spanish Network On Rare Diseases (CIBERER)
- Lenka Foretova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute
- Dita Berkova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute
- Anne-Marie Gerdes
- Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital
- Edith Olah
- Department of Molecular Genetics, National Institute of Oncology
- Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Christian F. Singer
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Yen Tan
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Annelie Augustinsson
- Department of Oncology, Clinical Sciences in Lund, Lund University Hospital
- Johanna Rantala
- Clinical Genetics, Karolinska Institutet
- Jacques Simard
- Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center
- Rita K. Schmutzler
- Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
- Roger L. Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Kelly-Anne Phillips
- The Sir Peter MacCallum Department of Oncology, University of Melbourne
- Mary Beth Terry
- Department of Epidemiology, Mailman School of Public Health and the Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center
- David Goldgar
- Department of Dermatology, University of Utah School of Medicine
- Flora E. van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute
- Thea M. Mooij
- Department of Epidemiology, Netherlands Cancer Institute
- Antonis C. Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge
- Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Matti A. Rookus
- Department of Epidemiology, Netherlands Cancer Institute
- Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University
- DOI
- https://doi.org/10.1186/s13058-023-01673-w
- Journal volume & issue
-
Vol. 25,
no. 1
pp. 1 – 13
Abstract
Abstract Introduction Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes. Patients and methods An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change. Results In the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04–1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66–0.84) and BRCA2 (HR 0.76, 95% CI 0.65–0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02–1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01–1.19, respectively). Conclusion Anthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.