Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Breast Cancer Research
  • View item
  • Home
  • ICR Divisions
  • Breast Cancer Research
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

Thumbnail
View/Open
Accepted version (447.9Kb)
Date
2019-06
ICR Author
Fletcher, Olivia
Swerdlow, Anthony
Author
Shu, X
Wu, L
Khankari, NK
Shu, X-O
Wang, TJ
Michailidou, K
Bolla, MK
Wang, Q
Dennis, J
Milne, RL
Schmidt, MK
Pharoah, PDP
Andrulis, IL
Hunter, DJ
Simard, J
Easton, DF
Zheng, W
Breast Cancer Association Consortium
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
Background In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
URI
https://repository.icr.ac.uk/handle/internal/3493
DOI
https://doi.org/10.1093/ije/dyy201
Collections
  • Breast Cancer Research
  • Genetics and Epidemiology
Subject
Breast Cancer Association Consortium
Humans
Breast Neoplasms
Diabetes Mellitus, Type 2
Obesity
Insulin
Blood Glucose
Body Mass Index
Waist-Hip Ratio
Adult
Aged
Middle Aged
Female
Obesity, Abdominal
Mendelian Randomization Analysis
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2018-09-06
License start date
2019-06
Citation
International journal of epidemiology, 2019, 48 (3), pp. 795 - 806

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.