A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese

Abstract

An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high‑risk region

“…Furthermore, the Arg/Arg genotype and reduced cancer risk has also been reported (34). A study performed in a Japanese population revealed that the Pro/Pro genotype at codon 72 was associated with increased risk of prostate cancer and its progression (35). Two separate meta-analyses by Jia et al (36) and Lao et al (37) suggested that the homozygote and heterozygote genotypes of Pro participated in the development of endometriosis in Asian and Caucasian populations.…”

Polymorphisms in the p53 pathway

“…In other studies, however, authors have found the opposite correlation, instead demonstrating an association between the P72 (lesser apoptotic) variant and increased risk for other cancer types, including cancer of the thyroid (Granja et al, 2004), nasopharynx (Tsai et al, 2002a, b;Tiwawech et al, 2003), prostate (Suzuki et al, 2003), skin (Chen et al, 2003), urogenital region (Kuroda et al, 2003), and lung Fan et al, 2000;Zhang et al, 2003). Still other groups have failed to demonstrate any association between codon 72 variants of p53 and cancer risk.…”

Prostate cancer incidence varies among males from different Y-chromosome lineages

“…Based on genomewide scans, such susceptibility loci and genetic alterations were attributed to chromosomes, 1,7,8,10,12,17,18,20, X, and the Y chromosome. [9][10][11][12][13][14] A large amount of data has been generated about alterations, aberrations, rearrangements, gain, or loss of Y-chromosome materials in prostate cancer using different techniques of molecular cytogenetics. [15][16][17][18][19][20] The simple fact that the Y chromosome and prostate cancer have male-specificity in common lead many researchers to investigate if there is Y involvement in such a male-specific cancer, however, yet there is no clear conclusions.…”