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 Kast¹, Esther M John^{2

3}, John L Hopper⁴, Nadine Andrieu^{5

6

7

8}, Catherine Noguès^{9

10}, Emmanuelle Mouret-Fourme⁶, Christine Lasset¹¹, Jean-Pierre Fricker¹², Pascaline Berthet¹³, Véronique Mari¹⁴, Lucie Salle¹⁵, Marjanka K Schmidt¹⁶, Margreet G E M Ausems¹⁷, Encarnacion B Gomez Garcia¹⁸, Irma van de Beek¹⁹, Marijke R Wevers²⁰, D Gareth Evans^{21

22

23}, Marc Tischkowitz²⁴, Fiona Lalloo²⁵, Jackie Cook²⁶, Louise Izatt²⁷, Vishakha Tripathi²⁸, Katie Snape²⁹, Hannah Musgrave³⁰, Saba Sharif³¹, Jennie Murray^{30

31

32

33}; EMBRACE Collaborators; Sarah V Colonna³⁴, Irene L Andrulis^{35

36}, Mary B Daly³⁷, Melissa C Southey^{38

39}, Miguel de la Hoya⁴⁰, Ana Osorio⁴¹, Lenka Foretova⁴², Dita Berkova⁴², Anne-Marie Gerdes⁴³, Edith Olah⁴⁴, Anna Jakubowska^{45

46}, Christian F Singer⁴⁷, Yen Tan⁴⁷, Annelie Augustinsson⁴⁸, Johanna Rantala⁴⁹, Jacques Simard⁵⁰, Rita K Schmutzler⁵¹, Roger L Milne^{4

52

53}, Kelly-Anne Phillips^{54

55}, Mary Beth Terry⁵⁶, David Goldgar⁵⁷, Flora E van Leeuwen⁵⁸, Thea M Mooij⁵⁸, Antonis C Antoniou⁵⁹, Douglas F Easton^{60

59}, Matti A Rookus⁵⁸, Christoph Engel⁶¹

Affiliations

¹ Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany. karin.kast@uk-koeln.de.
² Department of Epidemiology & Population Health and of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
³ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁵ INSERM U900, Paris, France.
⁶ Institut Curie, Paris, France.
⁷ Mines Paris Tech, Fontainebleau, France.
⁸ PSL Research University, Paris, France.
⁹ Aix Marseille Université, INSERM, IRD, SESSTIM, Marseille, France.
¹⁰ Département d'Anticipation et de Suivi Des Cancers, Oncogénétique Clinique, Institut Paoli-Calmettes, Marseille, France.
¹¹ Centre Léon Bérard, Lyon, France.
¹² CRLCC Paul Strauss, Strasbourg, France.
¹³ Centre François Baclesse, Caen, France.
¹⁴ Centre Antoine Lacassagne, Nice, France.
¹⁵ Oncogénétique Poitou-Charentes, Niort, France.
¹⁶ Division of Molecular Pathology, Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁷ Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
¹⁹ Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
²⁰ Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
²¹ The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust, Manchester, UK.
²² Genomic Medicine, Division of Evolution and Genomic Sciences, The University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
²³ Manchester Breast Centre, Oglesby Cancer Research Centre, The Christie, University of Manchester, Manchester, UK.
²⁴ Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
²⁵ Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁶ Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.
²⁷ Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
²⁸ Clinical Genetics Service, Guy's and St Thomas' NHS Foundation Trust, London, UK.
²⁹ Department of Clinical Genetics, St George's University Hospitals NHS Foundation Trust, London, UK.
³⁰ Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
³¹ West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK.
³² South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK.
³³ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³⁴ Department of Medicine and Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT, USA.
³⁵ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
³⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
³⁷ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
³⁸ Precision Medicine, School of Clinical Sciences at, Monash Health Monash University, Clayton, VIC, Australia.
³⁹ Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia.
⁴⁰ Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.
⁴¹ Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and Spanish Network On Rare Diseases (CIBERER), Madrid, Spain.
⁴² Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁴³ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁴ Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
⁴⁵ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴⁶ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
⁴⁷ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁴⁸ Department of Oncology, Clinical Sciences in Lund, Lund University Hospital, Lund, Sweden.
⁴⁹ Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
⁵⁰ Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec City, QC, Canada.
⁵¹ Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
⁵² Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁵³ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
⁵⁴ The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
⁵⁵ Department of Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia.
⁵⁶ Department of Epidemiology, Mailman School of Public Health and the Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
⁵⁷ Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁵⁸ Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁵⁹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁶⁰ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁶¹ Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.

PMID: 37340476
PMCID: PMC10280955
DOI: 10.1186/s13058-023-01673-w

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 et al. Breast Cancer Res. 2023.

. 2023 Jun 20;25(1):72.

doi: 10.1186/s13058-023-01673-w.

Authors

Affiliations

¹ Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany. karin.kast@uk-koeln.de.
² Department of Epidemiology & Population Health and of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
³ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁵ INSERM U900, Paris, France.
⁶ Institut Curie, Paris, France.
⁷ Mines Paris Tech, Fontainebleau, France.
⁸ PSL Research University, Paris, France.
⁹ Aix Marseille Université, INSERM, IRD, SESSTIM, Marseille, France.
¹⁰ Département d'Anticipation et de Suivi Des Cancers, Oncogénétique Clinique, Institut Paoli-Calmettes, Marseille, France.
¹¹ Centre Léon Bérard, Lyon, France.
¹² CRLCC Paul Strauss, Strasbourg, France.
¹³ Centre François Baclesse, Caen, France.
¹⁴ Centre Antoine Lacassagne, Nice, France.
¹⁵ Oncogénétique Poitou-Charentes, Niort, France.
¹⁶ Division of Molecular Pathology, Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁷ Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
¹⁹ Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
²⁰ Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
²¹ The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust, Manchester, UK.
²² Genomic Medicine, Division of Evolution and Genomic Sciences, The University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
²³ Manchester Breast Centre, Oglesby Cancer Research Centre, The Christie, University of Manchester, Manchester, UK.
²⁴ Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
²⁵ Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁶ Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.
²⁷ Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
²⁸ Clinical Genetics Service, Guy's and St Thomas' NHS Foundation Trust, London, UK.
²⁹ Department of Clinical Genetics, St George's University Hospitals NHS Foundation Trust, London, UK.
³⁰ Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
³¹ West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK.
³² South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK.
³³ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³⁴ Department of Medicine and Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT, USA.
³⁵ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
³⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
³⁷ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
³⁸ Precision Medicine, School of Clinical Sciences at, Monash Health Monash University, Clayton, VIC, Australia.
³⁹ Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia.
⁴⁰ Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.
⁴¹ Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and Spanish Network On Rare Diseases (CIBERER), Madrid, Spain.
⁴² Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁴³ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁴ Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
⁴⁵ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴⁶ Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.
⁴⁷ Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁴⁸ Department of Oncology, Clinical Sciences in Lund, Lund University Hospital, Lund, Sweden.
⁴⁹ Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
⁵⁰ Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec City, QC, Canada.
⁵¹ Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
⁵² Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁵³ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
⁵⁴ The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
⁵⁵ Department of Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia.
⁵⁶ Department of Epidemiology, Mailman School of Public Health and the Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
⁵⁷ Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁵⁸ Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁵⁹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁶⁰ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁶¹ Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.

PMID: 37340476
PMCID: PMC10280955
DOI: 10.1186/s13058-023-01673-w

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

References

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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

Affiliations

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

Authors

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Conflict of interest statement

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