Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of cytological abnormalities remission or persistence. These cofactors may be classified as environmental, epigenetic or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, the objective of this study was to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Sample group was divided in Remission (n=60) - presence of pre-neoplastic lesion at first meeting (T1), and normal cytology after six months of follow-up (T2), and Persistence (n=46) - presence of pre-neoplastic lesion at T1 and T2. Cervical samples were obtained for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5'-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide1494 in TS 3'-untranslated region (TS3'UTR). Genetic Risk Score (GRS) was calculated for analyze all genetic polymorphism simultaneously. Results: No differences were observed between Remission and Persistence groups of GRS, or genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, higher risk of persistence was observed among women presenting heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19 – 8.69), p=0.021], or polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71 – 24.70), p=0.006] of TS3’UTR. Conclusions: Presence of TS3’UTR polymorphism increased risk of persistence of cervical abnormalities. This genetic variant could be considered as potential marker of cervical carcinogenesis, assisting follow-up of women with persistent pre-neoplastic cervical lesions.
