Abstract
BackgroundHPV genotypes are the most common etiological factor for genital neoplasia. It would appear that sexually transmitted infections accompanied with HPV genotypes might have synergistic interactions in cancer progression. The genetic polymorphisms are involved in metabolizing carcinogens which may contribute to the susceptibility of developing genital cancers by less efficient or overly down metabolic pathways and cell signaling. MTHFR polymorphisms are related to several metabolic disorders and human cancers. We investigated the contribution of MTHFR 1298 and MTHFR 677 polymorphisms as potential risk factors for outcomes with HPV genotypes and STIs in Iranian population.Materials and MethodsAs a case–control study, MTHFR A1298C and C677T were assessed for SNPs analysis using a PCR–RFLP assay in 50 cervical intraepithelial neoplasia (CIN) cases, 98 HPV-positive subjects and 47 non-cancerous/non-HPV patients as healthy controls.ResultsFinding suggested a significant association between the MTHFR 1298 CC polymorphisms (OR = 3.5, 95% CI = 1.13–10.82, P ≤ 0.05) in women with CIN as compared to non-cancerous/non-HPV subjects. There was not a significant difference of MTHFR 677 between outcomes.DiscussionIt would seem MTHFR 1298 CC is more likely to be a potential risk factor for HPV–cervical cancer progression. Consequences support further attempts to understand the clinical manifestations of neoplasia related to genital infections and gene mutations.
Highlights
Cervical malignancies are one of the most common disorders in females worldwide
The methylenetetrahydrofolate reductase (MTHFR) A1298C and C677T genotype frequencies of HPV non-cancerous/ non-HPV group were in Hardy–Weinberg equilibrium. [Chi-square was 0.129, 0.21 and 1.43 (P value ≥ 0.05).] Comparison of the MTHFR 1298 and 677 polymorphisms between each of the cervical intraepithelial neoplasia subjects, HPV-infected cases and non-cancer/non-HPVs control indicated a significant difference in some genotypes
There was a significant association between the MTHFR 1298 CC polymorphisms in women with cervical intraepithelial neoplasia and non-cancerous/non-HPV control group
Summary
Cervical malignancies are one of the most common disorders in females worldwide. Approximately 86 percent of these cases occur in developing communities, where careHPV, prophylactic screening and a nationally organized program are not commonly available. Environmental conditions, coinfections, genetic patterns and epigenetic characteristics accompanied with HPV genotypes are major risk factors for genital malignancies and disorders [1,2,3]. Most sexually active women and men are infected at some points in their lives Additional microbial pathogens such as sexually transmitted infections (STIs) could increase the risk of cervical neoplasia induction [1]. Some single-nucleotide polymorphisms (SNPs) and STI, especially HPV infections, are considered predisposing factors for genital cancerous lesion progression [4, 5]. We investigated the contribution of MTHFR 1298 and MTHFR 677 polymorphisms as potential risk factors for outcomes with HPV genotypes and STIs in Iranian population. Consequences support further attempts to understand the clinical manifestations of neoplasia related to genital infections and gene mutations
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