Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Genetics and Epidemiology
  • View item
  • Home
  • ICR Divisions
  • Genetics and Epidemiology
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.

Thumbnail
View/Open
Accepted version (653.7Kb)
Date
2019-04
ICR Author
Eeles, Rosalind
Author
Qian, F
Wang, S
Mitchell, J
McGuffog, L
Barrowdale, D
Leslie, G
Oosterwijk, JC
Chung, WK
Evans, DG
Engel, C
Kast, K
Aalfs, CM
Adank, MA
Adlard, J
Agnarsson, BA
Aittomäki, K
Alducci, E
Andrulis, IL
Arun, BK
Ausems, MGEM
Azzollini, J
Barouk-Simonet, E
Barwell, J
Belotti, M
Benitez, J
Berger, A
Borg, A
Bradbury, AR
Brunet, J
Buys, SS
Caldes, T
Caligo, MA
Campbell, I
Caputo, SM
Chiquette, J
Claes, KBM
Margriet Collée, J
Couch, FJ
Coupier, I
Daly, MB
Davidson, R
Diez, O
Domchek, SM
Donaldson, A
Dorfling, CM
Eeles, R
Feliubadaló, L
Foretova, L
Fowler, J
Friedman, E
Frost, D
Ganz, PA
Garber, J
Garcia-Barberan, V
Glendon, G
Godwin, AK
Gómez Garcia, EB
Gronwald, J
Hahnen, E
Hamann, U
Henderson, A
Hendricks, CB
Hopper, JL
Hulick, PJ
Imyanitov, EN
Isaacs, C
Izatt, L
Izquierdo, Á
Jakubowska, A
Kaczmarek, K
Kang, E
Karlan, BY
Kets, CM
Kim, S-W
Kim, Z
Kwong, A
Laitman, Y
Lasset, C
Hyuk Lee, M
Won Lee, J
Lee, J
Lester, J
Lesueur, F
Loud, JT
Lubinski, J
Mebirouk, N
Meijers-Heijboer, HEJ
Meindl, A
Miller, A
Montagna, M
Mooij, TM
Morrison, PJ
Mouret-Fourme, E
Nathanson, KL
Neuhausen, SL
Nevanlinna, H
Niederacher, D
Nielsen, FC
Nussbaum, RL
Offit, K
Olah, E
Ong, K-R
Ottini, L
Park, SK
Peterlongo, P
Pfeiler, G
Phelan, CM
Poppe, B
Pradhan, N
Radice, P
Ramus, SJ
Rantala, J
Robson, M
Rodriguez, GC
Schmutzler, RK
Hutten Selkirk, CG
Shah, PD
Simard, J
Singer, CF
Sokolowska, J
Stoppa-Lyonnet, D
Sutter, C
Yen Tan, Y
Teixeira, RM
Teo, SH
Terry, MB
Thomassen, M
Tischkowitz, M
Toland, AE
Tucker, KM
Tung, N
van Asperen, CJ
van Engelen, K
van Rensburg, EJ
Wang-Gohrke, S
Wappenschmidt, B
Weitzel, JN
Yannoukakos, D
GEMO Study Collaborators
HEBON
EMBRACE
Greene, MH
Rookus, MA
Easton, DF
Chenevix-Trench, G
Antoniou, AC
Goldgar, DE
Olopade, OI
Rebbeck, TR
Huo, D
Show allShow less
Type
Journal Article
Metadata
Show full item record
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.
URI
https://repository.icr.ac.uk/handle/internal/3170
DOI
https://doi.org/10.1093/jnci/djy132
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
GEMO Study Collaborators
HEBON
EMBRACE
Humans
Breast Neoplasms
Genetic Predisposition to Disease
BRCA1 Protein
BRCA2 Protein
Body Mass Index
Body Height
Prognosis
Risk Factors
Mutation
Polymorphism, Single Nucleotide
Adult
Female
Mendelian Randomization Analysis
Research team
Oncogenetics
Language
eng
Date accepted
2018-06-29
License start date
2019-04
Citation
Journal of the National Cancer Institute, 2019, 111 (4), pp. 350 - 364

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.