Lockett Kristin L, Snowhite Isaac V, Hu Jennifer J
Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Cancer Lett. 2005 Apr 8;220(2):125-35. doi: 10.1016/j.canlet.2004.08.019.
Prostate cancer (CaP) is the most commonly diagnosed nonskin cancer and the second leading cause of cancer death in American men. Its etiology is not fully understood. Ethnicity/race and family history are associated with it, and incidence increases with age. As with other solid tumors, accumulation of mutations and decline in DNA repair during aging may lead to CaP. However, we believe that conducting a large population screening for every cancer susceptibility gene (e.g. DNA repair) is only meaningful, if we can predict to what extent genetic variants contribute to DNA-repair functional phenotype and CaP risk. This review focuses on the association between CaP and nucleotide excision repair (NER), because some of the DNA adducts generated by CaP-related carcinogens are removed by the NER pathway, and our previous data showed a significant association between lower NER capacity (NERC) and CaP risk. Many laboratories, including ours, have employed a variety of approaches to evaluate the functional significance of DNA-repair single-nucleotide polymorphisms (SNPs) in human cancer risk assessment. Genetic profiling and computational modeling that can predict NERC may have great potential for CaP-risk assessment, because the current NERC assay is quite labor intensive, costly, and therefore not suitable for population-based screening.
前列腺癌（CaP）是美国男性中最常被诊断出的非皮肤癌，也是癌症死亡的第二大主要原因。其病因尚未完全明确。种族和家族病史与之相关，且发病率随年龄增长而增加。与其他实体瘤一样，衰老过程中突变的积累和DNA修复能力的下降可能导致前列腺癌。然而，我们认为，只有当我们能够预测基因变异在多大程度上影响DNA修复功能表型和前列腺癌风险时，对每个癌症易感基因（如DNA修复基因）进行大规模人群筛查才有意义。本综述聚焦于前列腺癌与核苷酸切除修复（NER）之间的关联，因为一些与前列腺癌相关的致癌物产生的DNA加合物可通过NER途径清除，而且我们之前的数据显示较低的NER能力（NERC）与前列腺癌风险之间存在显著关联。包括我们实验室在内的许多实验室都采用了多种方法来评估DNA修复单核苷酸多态性（SNP）在人类癌症风险评估中的功能意义。能够预测NERC的基因谱分析和计算模型在前列腺癌风险评估中可能具有巨大潜力，因为目前的NERC检测相当耗费人力、成本高昂，因此不适合基于人群的筛查。
