Author:
Kast Karin,John Esther M.,Hopper John L.,Andrieu Nadine,Noguès Catherine,Mouret-Fourme Emmanuelle,Lasset Christine,Fricker Jean-Pierre,Berthet Pascaline,Mari Véronique,Salle Lucie,Schmidt Marjanka K.,Ausems Margreet G. E. M.,Garcia Encarnacion B. Gomez,van de Beek Irma,Wevers Marijke R.,Evans D. Gareth,Tischkowitz Marc,Lalloo Fiona,Cook Jackie,Izatt Louise,Tripathi Vishakha,Snape Katie,Musgrave Hannah,Sharif Saba,Murray Jennie,Colonna Sarah V.,Andrulis Irene L.,Daly Mary B.,Southey Melissa C.,de la Hoya Miguel,Osorio Ana,Foretova Lenka,Berkova Dita,Gerdes Anne-Marie,Olah Edith,Jakubowska Anna,Singer Christian F.,Tan Yen,Augustinsson Annelie,Rantala Johanna,Simard Jacques,Schmutzler Rita K.,Milne Roger L.,Phillips Kelly-Anne,Terry Mary Beth,Goldgar David,van Leeuwen Flora E.,Mooij Thea M.,Antoniou Antonis C.,Easton Douglas F.,Rookus Matti A.,Engel Christoph,
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.
Funder
German Cancer Aid
Federal Ministry of Education and Research
USA National Cancer Institute
Cancer Australia
Australian National Breast Cancer Foundation
National Health and Medical Research Council
the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia
Fondation de France and the Ligue Nationale Contre le Cancer
INCa as part of the European program ERA-NET on Translational Cancer Research
Dutch Cancer Society
The Netherlands Organisation of Scientific Research
The Pink Ribbon
BBMRI
Transcan
Cancer Research UK
NIHR Cambridge Biomedical Research Centre
MH CZ - DRO
FEDER funds and the Spanish Network on Rare Diseases
Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program and by the Canadian Breast Cancer Research Alliance
NIHR Manchester Biomedical Research Centre
Universitätsklinikum Köln
Publisher
Springer Science and Business Media LLC