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 χ² 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.

Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

“…Other genetic studies also confirmed that the Pro/Pro genotype of p53 codon 72 polymorphism may increase the risk of cervical cancer in Japanese populations and p53 gene polymorphisms appear to be related to a higher grade of cervical cancer (Ashton et al, 2009;Nunobiki et al, 2009). However, Zubor et al did not demonstrate any significant association between p53 codon 72 polymorphism and the risk of cervical cancer in Caucasians (Zubor et al, 2009). Therefore, the possible influence of p53 codon 72 polymorphism on p53 production as well as tumor development and progression in cervical cancer is still controversial.…”

The Arg72Pro Polymorphism of TP53 in Croatian Population

“…20,22,23 Arg72Pro polymorphism of TP53 gene appears to be very informative anthropological marker with characteristic ethnic pattern. Arg72Pro substitution has genotype frequencies in Europeans of ~60, 30 and 10 % for Arg/Arg, Arg/Pro and Pro/Pro, respectively.…”

“…2,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Whereas the Arg72Pro polymorphism is important for the tumor suppressor function of p53/p73 proteins, we investigated the genotypic frequency of p53 codon 72 polymorphism in the healthy Croatian population, and compared the frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes, as well as Arg and Pro alleles with the population of other countries worldwide.…”

Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk

“…Ashton et al (2009) showed that p53 gene polymorphisms appear to be related to a higher grade of EC. However, Zubor et al did not demonstrate any significant association between p53 codon 72 polymorphism and the risk of EC in Caucasian women (Zubor et al, 2009). Therefore, the possible influence of p53 codon 72 polymorphism on p53 production as well as tumor development and progression in EC is still controversial.…”

“…According to the inclusion criteria, only 10 case-control studies (Esteller et al, 1997;Peller et al, 1999;Agorastos et al, 2004;Roh et al, 2004;Niwa et al, 2005;Ueda et al, 2006;Ashton et al, 2009;Nunobiki et al, 2009;Zubor et al, 2009;Ghasemi et al, 2010) with full-text were included in this meta-analysis and 21 studies were excluded. The flow chart for the study selection is summarized in Figure 1.…”