The p53 Codon 72 Exon 4 BstUI Polymorphism and Endometrial Cancer in Caucasian Women

Abstract

OBJECTIVES: Studies on the association between the p53 Arg72Pro polymorphism and endometrial cancer have reported contrasting conclusions. With the exception of Asian subjects, data demonstrating the influence of this polymorphism on endometrial carcinogenesis in other races/ethnic groups, including Caucasians, are scarce. Thus, we aimed to investigate its role in the development of endometrial cancer and its association with prognostic markers. METHODS: A case-control study examining the p53 codon 72 polymorphism in a total of 451 samples (121 cancer patients, 330 healthy controls) using polymerase chain reaction and sequencing techniques was conducted. Genotypes were correlated with clinico-pathological factors and age. Logistic regression analyses were used to adjust for possible confounding variables, and data were evaluated using the Pearson chi(2) test. RESULTS: We found the Pro allele and genotype frequency to be insignificantly higher in cases than controls (Pro allele: 24.8 and 22.3%, respectively; genotypes: Arg/Pro 36.36 and 34.24%, Pro/Pro 6.61 and 5.15%, respectively). Logistic regression analysis revealed an increased risk for disease in carriers of the Pro allele, with an odds ratio (OR) of 1.13 [95% confidence interval (CI) 0.73-1.76] for heterozygotes and an OR of 1.36 (95% CI 0.56-3.30) for homozygotes. Furthermore, we noted a trend for Arg/Pro + Pro/Pro towards poor tumour differentiation, angioinvasion, pelvic lymph node spread and type II carcinomas, with ORs of 1.27 (95% CI 0.60-2.66), 1.24 (95% CI 0.67-2.30), 1.21 (95% CI 0.53-2.75) and 1.69 (95% CI 0.70-4.10), respectively. Additionally, the Pro genotype was associated with a lower risk for cancer in women with early menarche (OR 1.17, 95% CI 0.60-2.28) and late menopause (OR 0.70, 95% CI 0.30-1.63). Despite the increased or decreased risk observed for some variables, none of these trends were significant. CONCLUSIONS: Our data did not demonstrate any significant difference in the prevalence of the p53 Arg72Pro genotype between patients and controls, providing evidence that this polymorphism is only weakly associated with the risk of endometrial cancer and prognostic factors in Caucasian women.