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Body mass index and breast cancer survival: a Mendelian randomization analysis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Qi Guo
  • Stephen Burgess
  • Constance Turman
  • Manjeet K Bolla
  • Qin Wang
  • Michael Lush
  • Jean Abraham
  • Kristiina Aittomäki
  • Irene L Andrulis
  • Carmel Apicella
  • Volker Arndt
  • Myrto Barrdahl
  • Javier Benitez
  • Christine D Berg
  • Carl Blomqvist
  • Stig E Bojesen
  • Bernardo Bonanni
  • Judith S Brand
  • Hermann Brenner
  • Annegien Broeks
  • Barbara Burwinkel
  • Carlos Caldas
  • Daniele Campa
  • Federico Canzian
  • Jenny Chang-Claude
  • Stephen J Chanock
  • Suet-Feung Chin
  • Fergus J Couch
  • Angela Cox
  • Simon S Cross
  • Cezary Cybulski
  • Kamila Czene
  • Hatef Darabi
  • Peter Devilee
  • W Ryan Diver
  • Alison M Dunning
  • Helena M Earl
  • Diana M Eccles
  • Arif B Ekici
  • Mikael Eriksson
  • D Gareth Evans
  • Peter A Fasching
  • Jonine Figueroa
  • Dieter Flesch-Janys
  • Henrik Flyger
  • Susan M Gapstur
  • Mia M Gaudet
  • Graham G Giles
  • Sune F Nielsen
  • Børge G Nordestgaard
  • kConFab/AOCS Investigators
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftInternational Journal of Epidemiology
Vol/bind46
Udgave nummer6
Sider (fra-til)1814-1822
Antal sider9
ISSN0300-5771
DOI
StatusUdgivet - 1 dec. 2017

ID: 52337669