Is Type 2 Diabetes Causally Associated With Cancer Risk? Evidence From a Two-Sample Mendelian Randomization Study.


Type
Article
Change log
Authors
Kar, Siddhartha 
Carter, Paul 
Vithayathil, Mathew 
Mason, Amy M 
Abstract

We conducted a two-sample Mendelian randomization 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 and lower odds of esophageal cancer and melanoma but not associated with 16 other site-specific cancers or overall cancer. The odds ratios (ORs) were 1.13 (95% CI 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 esophageal cancer and melanoma, respectively. The association between T2DM and pancreatic cancer was also observed in a meta-analysis of this and a previous Mendelian randomization study (OR 1.08; 95% CI 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 current study found causal detrimental effects of T2DM on several cancers. We suggest reinforcing the cancer screening in T2DM patients to enable the early detection of cancer.

Description
Keywords
Blood Glucose, Diabetes Mellitus, Type 2, Early Detection of Cancer, Fasting, Genetic Predisposition to Disease, Humans, Insulin, Mendelian Randomization Analysis, Neoplasms, Risk
Journal Title
Diabetes
Conference Name
Journal ISSN
0012-1797
1939-327X
Volume Title
69
Publisher
American Diabetes Association
Rights
All rights reserved
Sponsorship
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MC_UU_00002/7)