Effects of four single nucleotide polymorphisms of EZH2 on cancer risk: a systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Although the relationship between several single nucleotide polymorphisms (SNPs) of the oncogene EZH2 and cancer risk has been assessed by some case-control studies, results of subsequent studies are controversial. Sample sizes from single-center studies are also limited, thereby providing unreliable findings. Hence, we conducted a comprehensive search and meta-analysis to evaluate the associations between EZH2 SNPs and cancer risk. MATERIALS AND METHODS: A comprehensive literature search for studies focusing on EZH2 SNPs and cancer risk was conducted on PubMed, Web of Science, Embase, and China National Knowledge Infrastructure online databases. Genotype data were extracted and examined through a meta-analysis, and pooled odds ratios (ORs) with 95% CIs were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 12.0. RESULTS: Twelve eligible studies were included in this meta-analysis. The association of 4 SNPs, namely, rs887569, rs2302427, rs3757441, and rs41277434, in the EZH2 locus with cancer risk was evaluated. Five studies (1,794 cases and 1,878 controls) indicated that rs887569 was related to a decreased cancer risk (CTTT/CC OR =0.849, 95% CI [0.740 to 0.973], P=0.019; TT/CCCT OR =0.793, 95% CI [0.654 to 0.962], P=0.019). Seven studies (2,408 cases and 2,910 controls) showed that rs2302427 was linked to a decreased cancer risk (GG/CC OR =0.562, 95% CI [0.400 to 0.792], P=0.001; CGGG/CC OR =0.856, 95% CI [0.748 to 0.980], P=0.024; GG/CCCG OR =0.733, 95% CI [0.571 to 0.940], P=0.015). No relationships were observed between rs3757441 or rs41277434 and cancer risk. CONCLUSION: rs887569 and rs2302427 in EZH2 may be correlated with a decreased cancer risk. Although rs3757441 and rs41277434 are independent risk factors of cancer, further large-scale and functional studies are warranted to validate our findings.