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, 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
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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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