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. 2020 Jul;69(7):1588-1596.
doi: 10.2337/db20-0084. Epub 2020 Apr 29.

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

Shuai Yuan  1   2 , Siddhartha Kar  3 , Paul Carter  4 , Mathew Vithayathil  5 , Amy M Mason  6   7 , Stephen Burgess  4   8 , Susanna C Larsson  9   2
Affiliations

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

Shuai Yuan et al. Diabetes. 2020 Jul.

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.

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Figures

Figure 1
Figure 1
Association between T2DM and overall cancer in UK Biobank with 75,037 cancer patients and 292,606 participants without cancer. Heterogeneity was observed in both analyses. There was no detected pleiotropy in MR-Egger analyses. Two and three outliers were detected and corrected in the MR-PRESSO analysis using 399 SNPs and 295 SNPs for T2DM, respectively. IVW, inverse variance weighted.
Figure 2
Figure 2
Associations between T2DM (399 SNPs) and 22 site-specific cancers in UK Biobank. All estimations were based on the inverse variance weighted method. ER, estrogen receptor; UKBB, UK Biobank.
Figure 3
Figure 3
Sensitivity analyses of the associations between T2DM and certain site-specific cancers in UK Biobank. Heterogeneity was observed in the analysis of uterine, liver, and melanoma cancer. There was detected pleiotropy in MR-Egger analysis of cervical cancer. One and three outliers was detected and corrected in the MR-PRESSO analysis of cervical and liver cancer, respectively. IVW, inverse variance weighted.
Figure 4
Figure 4
Meta-analysis of the association of T2DM with certain site-specific cancers. *Effect size in a study by Song et al. (34) was estimated in men and women separately. First author names appear for Cancer site & Study column. UKBB, UK Biobank.
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