Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk

Abstract

Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI). Cochran’s Q-test and I2 were used to study heterogeneity, based on which either a random or a fixed effect model was implemented. The meta-analysis identified 11 SNPs (from 10 genes) to be significantly associated with increased EC risk. Among these, seven SNPs were significant in at least three of the five genetic models, as well as three of the polymorphisms (rs1801320, rs11224561, and rs2279744) corresponding to RAD51, PGR, and MDM2 genes, which contained more than 1000 EC cases each and exhibited increased risk. The current meta-analysis indicates that polymorphisms associated with various hormone related genes—SULT1A1 (rs1042028), PGR (rs11224561), and CYP19A1 (rs10046 and rs4775936); DNA repair genes—ERCC2 (rs1799793), OGG1 (rs1052133), MLH1 (rs1800734), and RAD51 (rs1801320) as well as genes like MDM2 (rs2279744), CCND1 (rs9344), and SERPINE1 (rs1799889), are significantly associated with increased EC risk.

Superoxide Dismutase (rs2070424, rs4880, rs2536512) and Catalase (rs794316, rs1001179) SNPs and their Association with Breast Cancer Risk: Findings from a Hospital Based Case-Control Study

“…Single nucleotide polymorphisms (SNPs) are the most common genetic variations in human genome located in different region of genes. These SNPs can regulate oxidative stress, DNA repair, cell cycle, metabolism and regulate individual’s genetic susceptibility towards cancer [ 1 - 5 ]. Reactive oxygen species (ROS) are formed as a consequence of oxidative stress which alter normal cell function and harm cellular machinery which ultimately promote carcinogenesis [ 6 ].…”

“…The prevalence of BC in rural India is comparatively high where lack of knowledge, high use of tobacco, illiteracy unhealthy diet, limited resources for early detection and treatment are intensively described as responsible factors for BC carcinogenesis. Breast cancer genetics is heterogeneous and more complex where several genetic factors are linked with increased risk oxidative stress, DNA repair, cell cycle, metabolism and regulate individual's genetic susceptibility towards cancer [1][2][3][4][5]. Reactive oxygen species (ROS) are formed as a consequence of oxidative stress which alter normal cell function and harm cellular machinery which ultimately promote carcinogenesis [6].…”

The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan

“…In genomic studies, one of the most investigated polymorphisms is the G to C polymorphism in RAD51's promoter region, rs1801320 (G-135C) (42). Literature reports associate RAD51 rs1801320 genotypes with susceptibility to various cancers, including breast (43)(44)(45)(46)(47)(48)(49), laryngeal (50), colorectal (51,52), prostate (42), ovarian (46,53,54), cervical (55), endometrial (56,57), and glioblastoma (58).…”