Genetic, environmental and Clinical Factors Related to Treatment Failure of Cervical Precancerous Lesions in a Cohort of Brazilian Women

Abstract

Aims: To ascertain the risk of pre-cancerous treatment failure considering selected genetic, environmental, and clinical characteristics among Brazilian women. Study Design: A prospective study developed in a cohort of women treated for Cervical Intraepithelial Neoplasia (CIN) lesion. Place and Duration of Study: Gynecology Oncology day clinic of Brazilian National Cancer Institute, between October 2004 and May 2006. Methodology: We included 285 women (age range 18-75 years) with CIN submitted to lesion excision. All patients were interviewed at admission to identify epidemiological and clinical characteristics, having blood samples collected, and a colposcopic examination performed. TP53 polymorphism was ascertained using PCR-RFLP. After treatment, the study population was followed up with Pap-tests during two years. Treatment failure was evaluated using histological confirmation of any altered tissue. Kaplan-Meyer curves and Cox Proportional Risk Model were used for data analysis. Results: Frequencies of TP53 polymorphisms were: Arg72Pro genotype(Arg/Pro)-177(62.1%); Arg72 genotype(Arg/Arg)-55(19.3%); Pro genotype (Pro/Pro)-53(18.6%). Women with endocervical margins involvement showed an HR 7.01(1.73-28.44). Current smoking was statistically related to CIN treatment failure (HR:3.90,95%CI:1.28-11.91). Comparatively to Arg/Arg, the risks for treatment failure were: HR 1.51(95%CI:0.23-9.80) for Arg/Pro women; and HR:1.41 (95%CI:0.31-6.52) for Pro/Pro. Conclusion: Surgical margins involvement and current tobacco smoking presented independent risks for CIN treatment failure among the studied population. Pro/Pro genotype seems to be associated with CIN treatment failure.