Affiliation:
1. Leicester Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, U.K.
2. Leicester Cancer Research Centre, Leicester Royal Infirmary, University of Leicester, Leicester, U.K.
3. Leicester HPB Unit, Leicester General Hospital, Leicester, U.K.
4. National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, U.K.
Abstract
BACKGROUND AND PURPOSE
Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding.
DATA SOURCES AND STUDY SELECTION
PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality.
DATA EXTRACTION AND DATA SYNTHESIS
Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and <50% for other cancer incidences, and 92% for pancreatic cancer mortality.
LIMITATIONS
Biases other than unmeasured confounding were not analytically assessed.
CONCLUSIONS
Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.
Funder
University of Leicester
NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands
Leicester Biomedical Research Centre
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
92 articles.
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