Objectives: Methylenetetrahydrofolate reductase (MTHFR) gene is associated with DNA hypomethylation, an established hallmark of human cancer cells. The aim of this study was to examine the effect of MTHFR polymorphism C677T on cervical carcinogenesis in the context of other environmental factors, such as smoking, parity, and age at the first intercourse.
Methods: The study subjects were patients who were pathologically diagnosed with cervical neoplasia and who had a positive result for human papillomavirus (N = 462), and they were compared to normal healthy women as normal controls (N = 454). Genotypes of the patients and control samples were assayed by single base primer extension assay using SNapShot assay kit.
Results: Compared with MTHFR C/C, the odds ratio (95% confidence interval) for MTHFR T/T was 1.4 (0.9-2.3) for invasive cervical cancer and 1.3 (0.8-2.3) for cervical intraepithelial neoplasia (CIN) II or III. The risks for invasive cervical cancer were higher with less than 40 years old at diagnosis (2.1, 1.0-4.3), than with over 40 years old at diagnosis (1.2, 0.7-2.2). Current smoking women with early onset with MTHFR T/T had a 4.7 (0.6-36.2) times higher risk of cervical cancer. The risks of MTHFR T/T or C/T also increased for women with an early age of first intercourse or for women with two or more children, as compared with MTHFR C/C.
Conclusion: Polymorphisms of MTHFR are associated with a higher risk of developing cervical cancer, and in particular for an early onset of cervical carcinogenesis.