TP53 Genetic Polymorphisms and Environmental Risk Factors Associated with Cervical Carcinogenesis in A Cohort of Brazilian Women with Cervical Lesions

Abstract

The purpose of this study was to determine the prevalence of TP53 polymorphism at codon 72 and its association with environmental risk factors in a sample of women in Rio de Janeiro, Brazil. A cross-sectional study was conducted with 304 women with histological diagnoses of negative, precancerous, and cancerous lesions between October 2004 and May 2006. Antecedents of exposure to environmental risk factors were ascertained through an interview-administered questionnaire, and whenever indicated, colposcopy tests and lesion excisions were performed. Genomic DNA was extracted from leukocytes of peripheral blood subjects, and genotyping of TP53 polymorphism was conducted using polymerase chain reaction and restriction fragment-length polymorphism methods. Crude and adjusted odds ratios (OR) and their 95% confidence intervals (CI) were ascertained for selected risk factors and allelic groups among control, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL)/cancer strata, using logistic regression analysis. The TP53 polymorphism distribution in this population was 64 (21.1%) Arg/Arg, 55 (18.1%) Pro/Pro, and 185 (60.9%) Arg/Pro. Women who were heterozygous (Arg/Pro) showed an independent risk for cervical HSIL/cancer (adjusted OR: 1.92, 95%CI: 1.03–1.59, controlled for age, ethnicity, and age at menarche) compared to Pro/Pro genotypic women. Age at sexual onset up to 16 yr old (adjusted OR: 1.97, 95%CI: 1.18–3.3), lifelong 3–4 sexual partners (adjusted OR: 2.38, 95%CI: 1.32–4.28), current smoking (adjusted OR: 2.32, 95%CI: 1.31–4.13), and smoking more than 10 yr (adjusted OR: 2.52, 95%CI: 1.042–6.09) were found to be independent risk factors for cervical HSIL/cancer. Women possessing the Arg/Pro genotype presented a higher risk for HSIL/cancer development compared to Pro/Pro genotypic women in the sample studied after control for selected confounders. Early sexual onset, multiple sexual partners, and current and past tobacco smoking were independent risk factors for HSIL/ cancer development.

This study was supported by research grants relative to cervical cancer epidemiology from the Brazilian National Research Council-CNPq, from the Brazilian National Cancer Institute (INCA) and from the State of Rio de Janeiro Research Foundation (FAPERJ). This research was approved by the Ethical Committee of Brazilian National Cancer Institute, and informed consent was obtained from all study participants. The authors thank Dr. Miguel Angelo Martins Moreira and Michelle Oliveira e Silva, Brazilian National Cancer Institute, for their contribution on standardization of genetic procedures, Carlos Henrique Klein and Luciana Correia Alves, Fiocruz, for aiding with Bonferroni analysis, and Amy Elrod and Jennifer Fairchild for text review.