Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Cancer Causes Control. 2010 Feb;21(2):289-300. doi: 10.1007/s10552-009-9461-5. Epub 2009 Nov 10.
DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk.
Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 single-nucleotide polymorphisms (SNPs) in nine DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer.
There were no associations between these SNPs and overall risk of prostate cancer. Risks by genotype also did not vary by smoking or by family history of prostate cancer. Although two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced-stage tumors when comparing homozygous men carrying the minor versus major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors.
Overall, this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability, a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene-environment interactions may be warranted.
DNA 修复途径对于防止 DNA 损伤的积累和维持基因组稳定性至关重要。许多癌症都报道了该途径的改变。随着年龄的增长或由于种系遗传变异，氧化 DNA 损伤的增加或 DNA 修复能力的下降可能会影响前列腺癌的风险。
对两项基于人群的研究（1457 例病例和 1351 例对照）的汇总数据进行分析，以研究 9 个 DNA 修复基因（APEX1、BRCA2、ERCC2、ERCC4、MGMT、MUTYH、OGG1、XPC 和 XRCC1）中的 28 个单核苷酸多态性（SNP）与前列腺癌风险之间的关联。我们还探讨了这些关联是否因吸烟、家族史或前列腺癌的临床特征而有所不同。
这些 SNP 与前列腺癌的总体风险之间没有关联。基因型风险也不因吸烟或前列腺癌家族史而有所不同。虽然 BRCA2 中的两个 SNP（rs144848、rs1801406）和 ERCC2 中的两个 SNP（rs1799793、rs13181）在比较携带较小等位基因的纯合子男性时，与高 Gleason 评分或晚期肿瘤的风险较高有关，但在侵袭性和非侵袭性肿瘤之间，结果没有统计学上的显著差异。
总的来说，这项研究没有发现前列腺癌与 DNA 修复基因中的 SNP 之间存在关联。鉴于该途径的复杂性及其在维持基因组稳定性方面的关键作用，可能需要对 DNA 修复途径中的所有 150 个基因进行基于途径的分析，并探讨基因-环境相互作用。
