Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
Pathobiology. 2011;78(4):193-200. doi: 10.1159/000326767. Epub 2011 Jul 19.
The tumor suppressor gene p53 plays an important role in the stress response of the cell and is mutated in 50% of all human tumors. The p53 Arg72Pro single-nucleotide polymorphism (SNP) was found to be associated with an increased risk of various malignancies. Biochemical and biological differences between the 2 polymorphic variants of wild-type P53 might lead to distinct susceptibility to HPV- and non-HPV-induced tumors. For prostate cancer, only limited data are available, especially in the Caucasian population. Therefore, we determined the distribution of the Arg72Pro SNP in a Caucasian case-control study including 118 prostate cancer patients and 194 male controls without any malignancy using restriction fragment length polymorphism analysis. A subset of 33 tumors was tested for HPV infection, and no HPV DNA was found. Cases and controls showed similar distributions of alleles in the SNP (p = 0.720). Regarding the onset of the disease, patients diagnosed at ≤60 years of age and older patients (>60 years of age) showed a significant difference in genotype distribution (p = 0.035); there was also an increased occurrence of risk allele Pro72 in cases aged ≤60 years (p = 0.045). A subset of 64 prostate tumors was stained immunohistochemically for P53. 5 of 64 prostate tumors (7.8%) were positive for P53 expression, indicating integrity of the protein in the majority of cases. Genotype distribution showed no association with the Gleason score or additional histopathological characteristics. This study shows that the overall risk of prostate cancer was not associated with Arg72Pro SNP and HPV infection in our cohort. However, disease onset might be modulated by the p53 Pro72 allele, suggesting an important role of apoptosis regulation in prostate carcinogenesis.
抑癌基因 p53 在细胞应激反应中发挥重要作用，其突变存在于所有人类肿瘤的 50%中。p53 Arg72Pro 单核苷酸多态性（SNP）与各种恶性肿瘤的风险增加有关。野生型 P53 的两种多态变体之间的生化和生物学差异可能导致对 HPV 和非 HPV 诱导的肿瘤的不同易感性。对于前列腺癌，仅有有限的数据，特别是在白种人群中。因此，我们使用限制片段长度多态性分析，在包括 118 例前列腺癌患者和 194 例无恶性肿瘤的男性对照的白种人病例对照研究中，确定了 Arg72Pro SNP 的分布。对 33 例肿瘤进行 HPV 感染检测，未发现 HPV DNA。病例和对照组在 SNP 中的等位基因分布相似（p = 0.720）。关于疾病的发病，≤60 岁和>60 岁的患者在基因型分布上存在显著差异（p = 0.035）；≤60 岁的病例中风险等位基因 Pro72 的发生率也增加（p = 0.045）。对 64 例前列腺肿瘤进行了免疫组织化学染色，发现 64 例前列腺肿瘤中有 5 例（7.8%）P53 表达阳性，表明大多数病例的蛋白质完整性。基因型分布与 Gleason 评分或其他组织病理学特征无关。本研究表明，在我们的队列中，前列腺癌的总体风险与 Arg72Pro SNP 和 HPV 感染无关。然而，疾病的发病可能受到 p53 Pro72 等位基因的调节，提示细胞凋亡调节在前列腺癌发生中具有重要作用。
