Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2019-04-01
Date Accepted
2018-06-29
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.
Citation
Journal of the National Cancer Institute, 2019, 111 (4), pp. 350 - 364
Source Title
Publisher
OXFORD UNIV PRESS INC
ISSN
0027-8874
eISSN
1460-2105
Research Team
Oncogenetics