Deficient nucleotide excision repair capacity enhances human prostate cancer risk
Deficient nucleotide excision repair capacity enhances human prostate cancer risk
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DOI：
10.1158/0008-5472.can-03-2670
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发表时间：
2004-02-01
期刊：
影响因子：
11.2
通讯作者：
Case, LD
中科院分区：
文献类型：
--
作者：
Hu, JJ;Hall, MC;Case, LD
前列腺癌（CaP）是最常见的非皮肤癌，也是美国男性癌症死亡的第二大原因。CAP的病因尚未完全清楚。由于大多数的DNA加合物产生的一些CaP相关的致癌物，包括多环芳烃，杂环胺，农药，被删除的核苷酸切除修复（NER）途径，我们试点测试的假设，CaP是与缺乏NER能力（NERC），测量基于质粒的主机再激活试验。使用在一项正在进行的基于临床的病例对照研究中收集的冷冻保存的淋巴细胞，我们的结果显示，140例病例的平均NERC（平均值+/- SD，8.06 +/- 5.17）显著低于96例对照（9.64 +/- 5.49）（P = 0.03）。低于中位数的NERC与CaP风险之间存在显著相关性：在调整年龄、种族/民族、吸烟史、良性前列腺增生和家族史后，比值比（OR）为2.14; 95%置信区间（CI）为1.19-3.86。与老年受试者（大于或等于60岁）（OR，1.74; 95%CI，0.90-3.37）相比，年轻受试者（< 60岁）（OR，3.98; 95%CI，1.13-14.02）的这种相关性更强。当我们通过对照组的四分位数对NERC值进行分层时，在较低的NERC和升高的CaP风险之间存在显著的剂量依赖性关联（P（检验）（线性）（趋势），0.01）。与NERC的最高四分位数作为参考组相比，第75、50和25四分位数的校正OR分别为：1.09（95%CI，0.46-2.59）; 1.81（95%CI，0.77-4.27）;和2.63（95%CI，1.17-5.95）。这项初步研究是将NERC缺陷与人类CaP风险联系起来的第一个直接证据。
Prostate cancer (CaP) is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death in American men. The etiology of Cap is not fully understood. Because most of the DNA adducts generated by some CaP-related carcinogens, including polycyclic aromatic hydrocarbons, heterocyclic amines, and pesticides, are removed by the nucleotide excision repair (NER) pathway, we pilot tested the hypothesis that CaP is associated with deficient NER capacity (NERC), measured by a plasmid-based host reactivation assay. Using cryopreserved lymphocytes collected in an ongoing, clinic-based case-control study, our results showed that the mean NERC was significantly lower (P = 0.03) in 140 cases (mean +/- SD, 8.06 +/- 5.17) than in 96 controls (9.64 +/- 5.49). There was a significant association between below-median NERC and CaP risk: odds ratio (OR), 2.14; 95% confidence interval (CI), 1.19-3.86, after adjustment for age, race/ethnicity, smoking history, benign prostatic hyperplasia, and family history. This association was stronger in younger (< 60 years of age) subjects (OR, 3.98; 95 % CI, 1.13-14.02) compared with older (greater than or equal to60) subjects (OR, 1.74; 95% CI, 0.90-3.37). When we stratified NERC values by quartiles of controls, there was a significant dose-dependent association between lower NERC and elevated CaP risk (P (test) (for linear) (trend), 0.01). Compared with the highest quartile of NERC as the referent group, the adjusted ORs for the 75th, 50th, and 25th quartiles were: 1.09 (95 % CI, 0.46-2.59); 1.81 (95% CI, 0.77-4.27); and 2.63 (95% CI, 1.17-5.95), respectively. This pilot study is the first direct evidence associating deficient NERC with human CaP risk.