Abstract

BackgroundCervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. However, many environmental, genetical, and epigenetical cofactors can modulate viral infection and cervical carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. Nevertheless, studies with cervical cancer presented controversial results, and varied according to ethnicity. Thus, the aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer.MethodsA case-control study was performed with 150 histological cervical samples. Case group were divided in Cervical Intraepithelial Neoplasia (CIN) grade I (n = 30), CIN II (n = 30), CIN III (n = 30), and Squamous Cervical Carcinoma (SCC) (n = 30). Control group was composed by 30 samples without lesion, presenting cervicitis. HPV detection was performed by conventional Polymerase Chain Reaction (PCR) with SPF primers set, and by real-time PCR specific for HPV 16 and hr-HPV. MTHFR C677T polymorphism was analyzed by PCR followed by Restriction Fragment Length Polymorphism (RFLP).ResultsFrequency of MTHFR CC genotype was 72.7% (n = 109), CT 23.3% (n = 35) and TT 4.0% (n = 6). Polymorphic T allele frequency was 15.7%. No statistically significant association was observed between MTHFR C677T polymorphism and presence of pre-neoplastic or neoplastic cervical lesions. Similar frequencies of T allele was observed in control (23.3%) and cases (13.3%) groups (p = 0.174). In addition, there was no statistically significant association between MTHFR C677T polymorphism and viral infection, even considering hr-HPV or HPV 16 positivity.ConclusionMTHFR C677T polymorphism was not associated with cervical cancer and HPV infection.

Highlights

  • Cervical cancer has high prevalence and mortality rates in worldwide female population

  • Persistent infection with high-risk Human Papillomavirus is the main cause of cervical cancer, and 99.7% of cases are associated with the virus [3]

  • No statistically significant difference was observed between distribution of Methylenetetrahydrofolate reductase (MTHFR) genotypes or alleles and Human Papillomavirus (HPV) infection status (Fig. 3)

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Summary

Introduction

Cervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. The aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer. Lower incidence rates of this tumor occur in developed countries, where programs for Persistent infection with high-risk Human Papillomavirus (hr-HPV) is the main cause of cervical cancer, and 99.7% of cases are associated with the virus [3]. Presence of other factors in cervical cancer development is necessary in addition to HPV infection. Several genetics, epigenetics, and environmental factors had been studied [5, 6]

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