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Is Type 2 Diabetes Mellitus Causally Associated with Cancer Risk? Evidence from a Two-Sample Mendelian Randomisation Study

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posted on 29.04.2020 by Ada Admin, Shuai Yuan, Siddhartha Kar, Paul Carter, Mathew Vithayathil, Amy M. Mason, Stephen Burgess, Susanna C. Larsson
We conducted a two-sample Mendelian randomisation study to investigate the causal associations of type 2 diabetes mellitus (T2DM) with risk of overall cancer and 22 site-specific cancers. Summary-level data for cancer were extracted from the Breast Cancer Association Consortium and UK Biobank. Genetic predisposition to T2DM was associated with higher odds of pancreatic, kidney, uterine and cervical cancer, lower odds of oesophageal cancer and melanoma, but not associated with 16 other site-specific cancers or overall cancer. The odds ratios (95% confidence interval) were 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.08 (1.01, 1.15), 1.07 (1.01, 1.15), 0.89 (0.81, 0.98), and 0.93 (0.89, 0.97) for pancreatic, kidney, uterine, cervical, and oesophageal cancer and melanoma, respectively. The association between T2DM and pancreatic cancer was also observed in a meta-analysis of this and a previous Mendelian randomisation study (odds ratio 1.08; 1.02, 1.14; p=0.009). There was limited evidence supporting causal associations between fasting glucose and cancer. Genetically predicted fasting insulin levels were positively associated with cancers of the uterus, kidney, pancreas and lung. The present study found causal detrimental effects of T2DM on several cancers. We suggested to reinforce the cancers screening in T2DM patients to enable the early detection of cancer.


Funding for this study came from the Swedish Research Council (Vetenskapsrådet; Grant Number 2019-00977). Stephen Burgess is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z). Siddhartha Kar is supported by a Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme (C18281/A19169), and a Junior Research Fellowship from Homerton College, Cambridge.