Abstract
BackgroundThe association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis.MethodsThe previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping.ResultsNeither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72–0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69–1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53–1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99–1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97–1.51).ConclusionsThe MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.
Highlights
Cervical cancer is the third most frequently encountered cancer and the fourth leading cause of the women’s cancer death in the world, accounting for 9% (529,800) of the total newly-diagnosed cancer cases and 8% (275,100) of the total cancer deaths among females in 2008 [1]
As for the C677T polymorphism, no association was found between the polymorphism and the susceptibility to cervical lesions in all the genetic models (Table 3, dominant model: OR = 0.99, 95% confidence intervals (CIs) = 0.78–1.26, Figure 2A; recessive model: OR = 1.05, 95% CI = 0.80–1.38; additive model: OR = 0.97, 95% CI = 0.80–1.18,; CT vs. CC: OR = 0.97, 95% CI = 0.78–1.20, Figure 2B; TT vs. CC: OR = 1.06, 95% CI = 0.76–1.48, Figure 2C)
The subgroup analysis of the C677T polymorphisms in the histological stages of the cervical lesions revealed that the polymorphism was not associated with the risk of invasive cancer (ICC) or squamous intra-epithelial lesion. doi (SIL) in all the genetic models (Table 3)
Summary
Cervical cancer is the third most frequently encountered cancer and the fourth leading cause of the women’s cancer death in the world, accounting for 9% (529,800) of the total newly-diagnosed cancer cases and 8% (275,100) of the total cancer deaths among females in 2008 [1]. The virological, molecular, clinical and epidemiological studies have provided evidence that cervical cancer is a sequel to a long-term unresolved infection of certain genotypes of the Human Papilloma Virus (HPV) [2,3]. High-risk HPVs are known to infect cervical epithelium, with a subset of these being associated with preneoblastic lesions that can progress to cervical cancer. Despite the extremely high rate of infection by these viruses, the rate of cervical cancer, even in the prescreening area, has been less than one tenth that of exposure [4,5]. Other factors are important for cervical lesion development and progression such as a long-term use of hormonal contraceptives, multiparty, smoking, and some nutritional factors [6,7,8]. This study was designed to investigate their precise association using a large-scale meta-analysis
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