MTHFR C677T polymorphism was an ethnicity-dependent risk factor for cervical cancer development: evidence based on a meta-analysis.

Abstract

Many studies have studied the associations between 5, 10-methylene tetrahydrofolate reductase (MTHFR) polymorphisms and susceptibilities of cervical cancer and cervical intraepithelial neoplasia (CIN); however, the results were inconsistent. The aim of this study was to further assess the relationships by the method of meta-analysis. Two investigators independently searched the PubMed, Embase, Wang Fang (Chinese database) and CNKI (China National Knowledge Infrastructure), with latest update to July 1st, 2011. The pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of the associations by using fixed- or random-effect model. Ten case-control studies were included in this meta-analysis including a total of 1,803 cervical cancer or CIN cases and 2,363 controls. Pooled analyses showed that T allele of MTHFR C677T was significantly associated with increased CIN risk [OR (95 % CI): 1.28 (1.03-1.50) for CT vs. CC], especially for low-grade CIN risk. In addition, MTHFR C677T rather than A1298C polymorphism was associated with risk of cervical cancer. Stratifying analyses for ethnicity indicated that T allele of MTHFR C677T was associated with increased cervical cancer risk for Asian [OR (95 % CI): 1.56 (1.17-2.08) for TT vs. CC; 1.53 (1.19-1.96) for TT vs. C carriers] while decreased risk for Caucasian [OR (95 % CI): 0.63 (0.45-0.89) for TT vs. CC; 0.66 (0.56-0.79) for T carriers vs. CC]. This meta-analysis suggested that there was no association between MTHFR A1298C polymorphism and cervical cancer risk. However, MTHFR C677T was an ethnicity-dependent risk factor for cervical cancer occurrence. In addition, T allele of C677T was significantly associated with risk of low grade of CIN incidence. Because of modest limitations of our study, well-designed studies with large sample size were needed to confirm our findings in the future.