Purpose: Methylenetetrahydrofolate reductase (MTHFR) plays an important role in determining the proportions of folate coenzymes for DNA synthesis or DNA methylation. Published data on the association between the MTHFR polymorphisms and cervical risk are controversial. A meta-analysis was performed to assess whether the polymorphisms of MTHFR are associated with cervical cancer risk.
Methods: Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) for MTHFR C677T and MTHFR A1298C polymorphisms and cervical cancer were appropriately derived from fixed-effects or random effects models. Five different ORs were calculated: (1) allele contrast (C vs. T), (2) homozygous comparison (CC vs. TT), (3) heterozygous comparison (CC vs. CT), (4) dominant model (CC vs. CT+TT) and (5) recessive model (CC+CT vs. TT).
Results: A total of 13 studies, which included 12 studies for MTHFR C677T (2332 cases and 3000 controls) and five studies for A1298C polymorphisms (677 cases and 1191 controls), were enrolled in this meta-analysis. The pooled analyses revealed that MTHFR C677T polymorphism was not associated with cervical cancer risk; while the A1298C polymorphism had a significant association with increased cervical cancer risk in allele contrast, heterozygote comparison and dominant model (A C, OR = 0.84, 95 % CI = 0.71-0.98; AA vs. CC OR = 0.72, 95 % CI = 0.59-0.89; AA vs. AC+CC, OR = 0.72, 95 % CI = 0.59-0.88). The significant associations between MTHFR A1298C polymorphism and cervical cancer were found among Asians and population-based case-control studies.
Conclusions: This study indicated that the MTHFR C677T may be no associated with cervical cancer risk, and yet the MTHFR A1298C polymorphism may be a risk factor for cervical cancer.
Keywords: Cervical cancer; Meta-analysis; Methylenetetrahydrofolate reductase (MTHFR); Polymorphism.