Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Cancer Biol Ther. 2010 Jul 1;10(1):13-8. doi: 10.4161/cbt.10.1.12172.
Radiation therapy is a potentially curative, important treatment option in localized prostate cancer. However, at 8 years after radiation therapy, even in the best risk subset of patients, approximately 10% of patients will experience clinical disease recurrence. The identification of molecular markers of treatment success or failure may allow for the development of strategies to further improve treatment outcomes. Herein, we investigated five molecular markers of DNA repair. 513 patients with castrate-resistant prostate cancer (CRPC), including 284 patients who received radiotherapy, 229 patients without radiotherapy and 152 healthy individuals were genotyped for five polymorphisms in DNA excision repair genes:ERCC1 N118N (500C>T), XPD K751Q (2282A>C), XRCC1 R194W (685C>T), XRCC1 R399Q (1301G>A) and PARP1 V762A(2446T>C). The distribution of genetic polymorphisms in the patients with CRPC and in healthy controls was compared,and the association between the polymorphisms and overall survival was investigated. The polymorphisms evaluated did not show differences between the patient group and the healthy controls, nor did they show a trend toward an association with survival. However, in the radiation treated subgroup, the median survival time was associated with the XRCC1 haplotype. The median survival time was 11.75 years for patients with the R399Q AA /R194W CC haplotype,12.17 years for patients with the R399Q AG/R194W CC haplotype, 6.665 years for patients with the R399Q AG/R194WCT haplotype, and 6.21 years for patients with the R399Q GG/R194W CT haplotype (p = 0.034). This association was not found when all patients were investigated. We conclude that the genetic polymorphisms in XRCC1 may affect the outcome in patients who received radiotherapy for localized prostate cancer.
放射治疗是局限性前列腺癌的一种潜在的有治愈可能的重要治疗选择。然而，在放射治疗后 8 年，即使在风险最低的患者亚组中，约 10%的患者会出现临床疾病复发。鉴定治疗成功或失败的分子标志物可能会进一步制定改善治疗结果的策略。在此，我们研究了 5 个 DNA 修复的分子标志物。513 例去势抵抗性前列腺癌（CRPC）患者，包括 284 例接受放疗的患者，229 例未接受放疗的患者和 152 名健康个体，对 5 个 DNA 切除修复基因中的多态性进行了基因分型：ERCC1 N118N（500C>T）、XPD K751Q（2282A>C）、XRCC1 R194W（685C>T）、XRCC1 R399Q（1301G>A）和 PARP1 V762A（2446T>C）。比较了 CRPC 患者和健康对照者的遗传多态性分布，并研究了多态性与总生存期的关系。评估的多态性在患者组和健康对照组之间没有差异，也没有显示出与生存的关联趋势。然而，在放射治疗亚组中，中位生存时间与 XRCC1 单倍型相关。R399Q AA/R194W CC 单倍型患者的中位生存时间为 11.75 年，R399Q AG/R194W CC 单倍型患者的中位生存时间为 12.17 年，R399Q AG/R194W CT 单倍型患者的中位生存时间为 6.665 年，R399Q GG/R194W CT 单倍型患者的中位生存时间为 6.21 年（p = 0.034）。当所有患者都被研究时，没有发现这种关联。我们的结论是，XRCC1 中的遗传多态性可能会影响接受局限性前列腺癌放射治疗的患者的结局。
