Associação dos polimorfismos nos genes de reparo APE-1 (Asp148Glu) e PARP-1 (Val762Glu) com neoplasia intraepitelial cervical causadas pelo papilomavirus humano

Abstract

The high-grade cervical intraepithelial neoplasia disease (CIN) is the pre-cursor lesion of cervical cancer, the second most common cancer in women worldwide. Repair enzymes are important for genomic integrity and polymorphism in genes of DNA base excision repair (BER) enzymes can be relevant for cervical lesions susceptibility. Therefore, this study aimed to investigate the association of polymorphisms in BER genes APE-1 T2197G (Asp148Glu) and PARP-1 A40676G (Val762Ala) in cervical pre-cursor lesions, associating with tabaco smoking, alcohol consummation, age of beginning sexual activity and number of sexual partners per year. Materials and Methods - This case-control study included 203 women. Among the104 patients with biopsy indication, 75 were CIN positive and 29 CIN negative. The remaining 99 cases were considered control group. The polymorphisms for the DNA repair genes, APE-1 T > G and PARP-1 T > C was determined by PCR-RFLP. Results - The patients included in the study were aged 14-50 years (median 24 years). Among the CIN (+) cases, 66.7% were CIN 33.3% and I were CIN II/CIN III. No association was observed for APE-1 genotypes, but a statically low frequency of PARP-1 heterozygous genotype was associated to CIN I compared to the control group. Considering the risk factors, the PARP-1 TC genotype conferred a protection for CIN development, considering alcohol consummation (p = 0.038), onset sexual life before 18 years old (p = 0.044) and 0-1 number of partners (p = 0.001) for CIN development when compared control with CIN (+). Besides, the PARP-1 TC genotype conferred a protection for CIN development among patients who had low exposure to risk and among patients who beginning sexual life before 18 years old when compared to PARP-1 TT genotype. This last result were also observed when CIN (-) were considered as control, however, a risk was observed among the patients who reported having more than >1 sexual partner/year. Taking in account the risk factors exposure, having as reference the less exposure, it was observed that the TT genotype give a protection for CIN development for tobacco users (p = 0.017; OR = 0.100) and for patients who reported having more than one sexual partner (p = 0.000; OR=0.063). Considering the CIN subtypes, low frequency of TC genotype was observed in CIN I patients among the patients who have 0-1 sexual partner/year (p = 0.003; OR = 0.150) and a risk among patients who had >1 partner/year, (p= 0.015; OR = 28.000). Conclusion - This data suggest that the efficiency of the DNA repair involving PARP-1 is a balance between genotype and exposure of the risk factor as smoking and number of partner, where the efficiency of the heterozygous genotype for DNA repair is dependent of the risk exposure. This study add data for the association for PARP-1 Val762Ala (T40676C) polymorphism and CIN and was the first to include the APE-1 Asp148Glu (T2197G) genotype and CIN.