The Causal Relationship between Type 2 Diabetes Mellitus and Ovarian Cancer: Two-Sample Mendelian Randomization

Abstract

Aims: This research aimed at determining the causal relationship between type 2 diabetes mellitus (T2DM) and ovarian cancer using two-sample Mendelian randomization technique. This is because there is an assumption that type 2 diabetes mellitus (T2DM) has a causal relationship with ovarian cancer due to the alarming rising incidence statistics. Study design: This study used a two-sample Mendelian Randomization (MR) design to undertake the causal relationship investigation. Mendelian randomization technique uses genetic variants as instrumental variables, which undergo random allocation at conception and are non-modifiable. This makes it not to be affected by confounding factors and reverse causation. The MR techniques employed are MR-Egger and Inverse Variance Weighted (IVW.) Data sources: The outcome (ovarian cancer) summary statistics was retrieved from Ovarian Cancer Association Consortium (OCAC), which has 66,450 samples (number of cases=25,509, number of controls=40,941) of European population. The exposure (T2DM) summary genetic data came from DIAGRAM plus Metabochip consortium which involved approximately 149,821 samples (number of cases=34,840, number of controls=114,981) of mixed population. Results: The study indicated that there was no evidence of causal relationship between T2DM and ovarian cancer (MR-Egger: b= -0.0476, se = 0.0619, p-value = 0.4479, IVW: b = -0.0165, se = 0.0257, p-value = 0.5217). The odds ratios indicated that the two-sample Mendelian randomization had the power to detect 0.0464 and 0.0164 decrease in variability per 1 SD for MR-Egger and IVW respectively (MR-Egger: OR = 0.9536, CI: 0.8447, 1.0765, IVW: OR = 0.9836, CI: 0.9352, 1.0345). Conclusion: This approach alleviated the usual problem of reverse causation and confounding factors hence depicting clearly that there is no causal relationship between T2DM and Ovarian cancer.