Abstract
Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.
Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.
Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).
Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | International Journal of Epidemiology |
| Vol/bind | 46 |
| Udgave nummer | 6 |
| Sider (fra-til) | 1814-1822 |
| ISSN | 0300-5771 |
| DOI | |
| Status | Udgivet - 2017 |
Adgang til dokumentet
- 10.1093/ije/dyx131Licens: CC BY
- Body mass index and breast cancer survival: a Mendelian randomization analysisForlagets udgivne version, 313 KBLicens: CC BY
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Body mass index and breast cancer survival : a Mendelian randomization analysis. / Guo, Qi; Burgess, Stephen; Turman, Constance; Bolla, Manjeet K; Wang, Qin; Lush, Michael; Abraham, Jean; Aittomäki, Kristiina; Andrulis, Irene L; Apicella, Carmel; Arndt, Volker; Barrdahl, Myrto; Benitez, Javier; Berg, Christine D; Blomqvist, Carl; Bojesen, Stig E; Bonanni, Bernardo; Brand, Judith S; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Caldas, Carlos; Campa, Daniele; Canzian, Federico; Chang-Claude, Jenny; Chanock, Stephen J; Chin, Suet-Feung; Couch, Fergus J; Cox, Angela; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Diver, W Ryan; Dunning, Alison M; Earl, Helena M; Eccles, Diana M; Ekici, Arif B; Eriksson, Mikael; Evans, D Gareth; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Flyger, Henrik; Gapstur, Susan M; Gaudet, Mia M; Giles, Graham G; Glendon, Gord; Grip, Mervi; Gronwald, Jacek; Haeberle, Lothar; Hall, Per; Hamann, Ute; Hankinson, Susan; Hartikainen, Jaana M; Hein, Alexander; Hiller, Louise; Hogervorst, Frans B; Holleczek, Bernd; Hooning, Maartje J; Hoover, Robert N; Humphreys, Keith; Hunter, David J; Hüsing, Anika; Jakubowska, Anna; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kataja, Vesa; kConFab/AOCS Investigators; Knight, Julia A; Koppert, Linetta B; Kosma, Veli-Matti; Kristensen, Vessela N; Lambrechts, Diether; Marchand, Loic Le; Li, Jingmei; Lindblom, Annika; Lindström, Sara; Lissowska, Jolanta; Lubinski, Jan; Machiela, Mitchell J; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Federik; Martens, John WM; McLean, Catriona; Menéndez, Primitiva; Milne, Roger L; Mulligan, Anna Marie; Muranen, Taru A; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Nordestgaard, Børge G; Olson, Janet E; Perez, Jose IA; Peterlongo, Paolo; Phillips, Kelly-Anne; Poole, Christopher J; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rüdiger, Thomas; Rudolph, Anja; Sawyer, Elinor J; Schumacher, Fredrick; Seibold, Petra; Seynaeve, Caroline; Shah, Mitul; Smeets, Ann; Southey, Melissa C; Tollenaar, Rob A E M; Tomlinson, Ian; Tsimiklis, Helen; Ulmer, Hans Ulrich; Vachon, Celine; van den Ouweland, Ans MW; Van't Veer, Laura J; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Pilar Zamora, M; Chenevix-Trench, Georgia; Dörk, Thilo; Easton, Douglas F.; García-Closas, Montserrat; Kraft, Peter; Hopper, John L; Zheng, Wei; Schmidt, Marjanka K; Pharoah, Paul DP.
I: International Journal of Epidemiology, Bind 46, Nr. 6, 2017, s. 1814-1822.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Body mass index and breast cancer survival
T2 - a Mendelian randomization analysis
AU - Guo, Qi
AU - Burgess, Stephen
AU - Turman, Constance
AU - Bolla, Manjeet K
AU - Wang, Qin
AU - Lush, Michael
AU - Abraham, Jean
AU - Aittomäki, Kristiina
AU - Andrulis, Irene L
AU - Apicella, Carmel
AU - Arndt, Volker
AU - Barrdahl, Myrto
AU - Benitez, Javier
AU - Berg, Christine D
AU - Blomqvist, Carl
AU - Bojesen, Stig E
AU - Bonanni, Bernardo
AU - Brand, Judith S
AU - Brenner, Hermann
AU - Broeks, Annegien
AU - Burwinkel, Barbara
AU - Caldas, Carlos
AU - Campa, Daniele
AU - Canzian, Federico
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J
AU - Chin, Suet-Feung
AU - Couch, Fergus J
AU - Cox, Angela
AU - Cross, Simon S
AU - Cybulski, Cezary
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Devilee, Peter
AU - Diver, W Ryan
AU - Dunning, Alison M
AU - Earl, Helena M
AU - Eccles, Diana M
AU - Ekici, Arif B
AU - Eriksson, Mikael
AU - Evans, D Gareth
AU - Fasching, Peter A
AU - Figueroa, Jonine
AU - Flesch-Janys, Dieter
AU - Flyger, Henrik
AU - Gapstur, Susan M
AU - Gaudet, Mia M
AU - Giles, Graham G
AU - Glendon, Gord
AU - Grip, Mervi
AU - Gronwald, Jacek
AU - Haeberle, Lothar
AU - Hall, Per
AU - Hamann, Ute
AU - Hankinson, Susan
AU - Hartikainen, Jaana M
AU - Hein, Alexander
AU - Hiller, Louise
AU - Hogervorst, Frans B
AU - Holleczek, Bernd
AU - Hooning, Maartje J
AU - Hoover, Robert N
AU - Humphreys, Keith
AU - Hunter, David J
AU - Hüsing, Anika
AU - Jakubowska, Anna
AU - Jukkola-Vuorinen, Arja
AU - Kaaks, Rudolf
AU - Kabisch, Maria
AU - Kataja, Vesa
AU - kConFab/AOCS Investigators
AU - Knight, Julia A
AU - Koppert, Linetta B
AU - Kosma, Veli-Matti
AU - Kristensen, Vessela N
AU - Lambrechts, Diether
AU - Marchand, Loic Le
AU - Li, Jingmei
AU - Lindblom, Annika
AU - Lindström, Sara
AU - Lissowska, Jolanta
AU - Lubinski, Jan
AU - Machiela, Mitchell J
AU - Mannermaa, Arto
AU - Manoukian, Siranoush
AU - Margolin, Sara
AU - Marme, Federik
AU - Martens, John WM
AU - McLean, Catriona
AU - Menéndez, Primitiva
AU - Milne, Roger L
AU - Mulligan, Anna Marie
AU - Muranen, Taru A
AU - Nevanlinna, Heli
AU - Neven, Patrick
AU - Nielsen, Sune F
AU - Nordestgaard, Børge G
AU - Olson, Janet E
AU - Perez, Jose IA
AU - Peterlongo, Paolo
AU - Phillips, Kelly-Anne
AU - Poole, Christopher J
AU - Pylkäs, Katri
AU - Radice, Paolo
AU - Rahman, Nazneen
AU - Rüdiger, Thomas
AU - Rudolph, Anja
AU - Sawyer, Elinor J
AU - Schumacher, Fredrick
AU - Seibold, Petra
AU - Seynaeve, Caroline
AU - Shah, Mitul
AU - Smeets, Ann
AU - Southey, Melissa C
AU - Tollenaar, Rob A E M
AU - Tomlinson, Ian
AU - Tsimiklis, Helen
AU - Ulmer, Hans Ulrich
AU - Vachon, Celine
AU - van den Ouweland, Ans MW
AU - Van't Veer, Laura J
AU - Wildiers, Hans
AU - Willett, Walter
AU - Winqvist, Robert
AU - Pilar Zamora, M
AU - Chenevix-Trench, Georgia
AU - Dörk, Thilo
AU - Easton, Douglas F.
AU - García-Closas, Montserrat
AU - Kraft, Peter
AU - Hopper, John L
AU - Zheng, Wei
AU - Schmidt, Marjanka K
AU - Pharoah, Paul DP
N1 - © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association
PY - 2017
Y1 - 2017
N2 - Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
AB - Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
U2 - 10.1093/ije/dyx131
DO - 10.1093/ije/dyx131
M3 - Journal article
C2 - 29232439
VL - 46
SP - 1814
EP - 1822
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
SN - 0300-5771
IS - 6
ER -