Mitochondrial ribosomal protein L14 (MRPL14) significantly correlated with decreased risk of endometrioid endometrial cancer: A two-sample Mendelian randomization study

Abstract

Background The incidence of endometrial cancer (EC)is constantly rising, but its mortality has not been improved in decades. Understanding the molecular mechanism of EC may improve the early diagnosis and develop more targeted therapies. Mitochondrial dysfunction has been currently reported to impact the pathogenesis of various cancers. Thus, this study investigated whether mitochondrial proteins contributed to the development of EC. Methods Using meta-analyses data from genome-wide association studies (GWAS), we conducted a two-sample Mendelian randomization (MR) study on 63 mitochondrial proteins and endometrioid EC (EEC). Inverse-variance weighted (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression approaches were applied. The outcome measure consisted of a GWAS dataset for EEC, comprising a total of 54,884 individuals (8,758 cases and 46,126 controls). Results Of 63 mitochondrial proteins, mitochondrial ribosomal protein L14 (MRPL14) presented a causal association with the decreased susceptibility to EEC by the IVW analysis (MRPL14; odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.77–0.99, p = 0.039), although neither weighted median method nor MR-Egger regression achieved the same significance. Through Cochran's Q test and visual inspection via funnel plot, the assessment of heterogeneity found no evidence of heterogeneity or asymmetry in our findings, suggesting the absence of directional pleiotropy. Conclusion This MR study found MRPL14 was causally correlated with decreased risk of EEC, implying a novel perspective to understand the mechanism of this malignancy. Further validation is warranted to clarify the effect of MPRL14 in endometrial disorders.