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Association of type 2 diabetes with cancer: A meta-analysis with bias analysis for unmeasured confounding in 151 cohorts comprising 32 million people

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posted on 17.07.2020 by Suping Ling, Karen Brown, Joanne K Miksza, Lynne Howells, Amy Morrison, Eyad Issa, Thomas Yates, Kamlesh Khunti, Melanie J Davies, Francesco Zaccardi
Background: Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial.

Purpose: To assess how robust are the observational associations between (T2D) and cancer to unmeasured confounding.

Data sources: PubMed, Web of Science, and the Cochrane library were systematically searched on January 10th, 2019.

Study selection: Observational studies investigating associations between T2D and cancer incidence or mortality.

Data extraction: Cohort-level relative risk (RR).

Data Synthesis: 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 mortality of 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 less than 50% for other cancer incidence, 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.

Funding

The Leicester Real World Evidence Unit is funded by University of Leicester, NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands, and Leicester Biomedical Research Centre. This project was supported by the Leicester Institute of Advanced Studies (Tiger team). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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