Type 2 diabetes and cancer: an umbrella review of observational and Mendelian randomisation studies
File(s)
Accepted version
Author(s)
Pearson-Stuttard, Jonathan
Papadimitriou, Nikos
Markozannes, Georgios
Cividini, Sofia
Kakourou, Artemisia
Type
Journal Article
Abstract
Background Type 2 diabetes(T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarise the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomisation(MR) studies. Methods We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk. Results We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma. Conclusions We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial and pancreatic cancer. Impact Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung and cervical cancer.
Date Issued
2021-06-01
Date Acceptance
2021-02-25
Citation
Cancer Epidemiology, Biomarkers and Prevention, 2021, 30 (6), pp.1218-1228
ISSN
1055-9965
Publisher
American Association for Cancer Research
Start Page
1218
End Page
1228
Journal / Book Title
Cancer Epidemiology, Biomarkers and Prevention
Volume
30
Issue
6
Copyright Statement
© 2021 American Association for Cancer Research. This is the Accepted Manuscript version of a published work appearing in Cancer Epidemiology, Biomarkers and Prevention, https://doi.org/10.1158/1055-9965.EPI-20-1245
Sponsor
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33737302
PII: 1055-9965.EPI-20-1245
Grant Number
203928/Z/16/Z
Subjects
Epidemiology
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-03-18