Height and body mass index as modifiers of breast cancer risk in BRCA1/2 mutation carriers: A Mendelian randomization study Journal Article


Authors: Qian, F.; Wang, S.; Mitchell, J.; McGuffog, L.; Barrowdale, D.; Leslie, G.; Oosterwijk, J. C.; Chung, W. K.; Evans, D. G.; Engel, C.; Kast, K.; Aalfs, C. M.; Adank, M. A.; Adlard, J.; Agnarsson, B. A.; Aittomäki, K.; Alducci, E.; Andrulis, I. L.; Arun, B. K.; Ausems, M. G. E. M.; Azzollini, J.; Barouk-Simonet, E.; Barwell, J.; Belotti, M.; Benitez, J.; Berger, A.; Borg, A.; Bradbury, A. R.; Brunet, J.; Buys, S. S.; Caldes, T.; Caligo, M. A.; Campbell, I.; Caputo, S. M.; Chiquette, J.; Claes, K. B. M.; Collée, J. M.; Couch, F. J.; Coupier, I.; Daly, M. B.; Davidson, R.; Diez, O.; Domchek, S. M.; Donaldson, A.; Dorfling, C. M.; Eeles, R.; Feliubadaló, L.; Foretova, L.; Fowler, J.; Friedman, E.; Frost, D.; Ganz, P. A.; Garber, J.; Garcia-Barberan, V.; Glendon, G.; Godwin, A. K.; Gómez Garcia, E. B.; Gronwald, J.; Hahnen, E.; Hamann, U.; Henderson, A.; Hendricks, C. B.; Hopper, J. L.; Hulick, P. J.; Imyanitov, E. N.; Isaacs, C.; Izatt, L.; Izquierdo, Á; Jakubowska, A.; Kaczmarek, K.; Kang, E.; Karlan, B. Y.; Kets, C. M.; Kim, S. W.; Kim, Z.; Kwong, A.; Laitman, Y.; Lasset, C.; Hyuk Lee, M.; Won Lee, J.; Lee, J.; Lester, J.; Lesueur, F.; Loud, J. T.; Lubinski, J.; Mebirouk, N.; Meijers-Heijboer, H. E. J.; Meindl, A.; Miller, A.; Montagna, M.; Mooij, T. M.; Morrison, P. J.; Mouret-Fourme, E.; Nathanson, K. L.; Neuhausen, S. L.; Nevanlinna, H.; Niederacher, D.; Nielsen, F. C.; Nussbaum, R. L.; Offit, K.; Olah, E.; Ong, K. R.; Ottini, L.; Park, S. K.; Peterlongo, P.; Pfeiler, G.; Phelan, C. M.; Poppe, B.; Pradhan, N.; Radice, P.; Ramus, S. J.; Rantala, J.; Robson, M.; Rodriguez, G. C.; Schmutzler, R. K.; Hutten Selkirk, C. G.; Shah, P. D.; Simard, J.; Singer, C. F.; Sokolowska, J.; Stoppa-Lyonnet, D.; Sutter, C.; Tan, Y. Y.; Teixeira, R. M.; Teo, S. H.; Terry, M. B.; Thomassen, M.; Tischkowitz, M.; Toland, A. E.; Tucker, K. M.; Tung, N.; van Asperen, C. J.; van Engelen, K.; van Rensburg, E. J.; Wang-Gohrke, S.; Wappenschmidt, B.; Weitzel, J. N.; Yannoukakos, D.; GEMO Study Collaborators; HEBON; EMBRACE; Greene, M. H.; Rookus, M. A.; Easton, D. F.; Chenevix-Trench, G.; Antoniou, A. C.; Goldgar, D. E.; Olopade, O. I.; Rebbeck, T. R.; Huo, D.
Article Title: Height and body mass index as modifiers of breast cancer risk in BRCA1/2 mutation carriers: A Mendelian randomization study
Abstract: BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 111
Issue: 4
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2019-04-01
Start Page: 350
End Page: 364
Language: English
DOI: 10.1093/jnci/djy132
PUBMED: 30312457
PROVIDER: scopus
PMCID: PMC6449171
DOI/URL:
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    521 Offit
  2. Mark E Robson
    372 Robson