Wei Q, Cheng L, Hong W K, Spitz M R
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1996 Sep 15;56(18):4103-7.
Although lung cancer is the paradigm of a tobacco-induced malignancy, host-specific factors modulate susceptibility to tobacco carcinogenesis. Variations in DNA repair may influence the rate of removal of DNA damage and of fixation of mutations. To test the hypothesis that genetically determined DNA repair capacity (DRC) modulates lung cancer susceptibility, we conducted a pilot case-control study of 51 patients with newly diagnosed, previously untreated lung cancer and 56 controls identified from local community centers and frequency matched to the cases on age, sex, and ethnicity. The subjects were ascertained and interviewed for an ongoing molecular epidemiological investigation of lung cancer susceptibility. We measured DRC in the subjects' peripheral blood lymphocytes by using the host-cell reactivation assay, which measures cellular reactivation of a reporter gene damaged by exposure to 75 microM benzo(a)pyrene diol epoxide. The mean level of DRC in cases (3.3%) was significantly lower than that in controls (5.1%) (P < 0.01). Only nine cases (18%) had DNA repair levels greater than the median value of repair in the controls. This median level of DRC in controls was used as the cutoff value for calculating the odds ratios. After adjustment for age, sex, ethnicity, and smoking status, the cases were five times more likely than the controls to have reduced DRC (odds ratio, 5.7; 95% confidence interval, 2.1-15.7). Younger cases (< 65 years) and smokers were more likely than controls to have reduced DRC. These findings suggest that individuals with reduced DRC are at an increased risk of developing lung cancer.
尽管肺癌是烟草诱导的恶性肿瘤的典型代表，但宿主特异性因素会调节对烟草致癌作用的易感性。DNA修复的变异可能会影响DNA损伤的清除速率和突变的固定。为了检验基因决定的DNA修复能力（DRC）调节肺癌易感性这一假说，我们进行了一项前瞻性病例对照研究，研究对象包括51例新诊断的、未经治疗的肺癌患者以及56例从当地社区中心招募的对照，后者在年龄、性别和种族方面与病例进行了频率匹配。这些受试者是为正在进行的肺癌易感性分子流行病学调查而确定并接受访谈的。我们通过宿主细胞再激活试验来测量受试者外周血淋巴细胞中的DRC，该试验测量的是暴露于75微摩尔苯并(a)芘二醇环氧化物后受损报告基因的细胞再激活情况。病例组的DRC平均水平（3.3%）显著低于对照组（5.1%）（P < 0.01）。只有9例病例（18%）的DNA修复水平高于对照组的修复中值。对照组的DRC中值水平被用作计算比值比的临界值。在对年龄、性别、种族和吸烟状况进行调整后，病例组的DRC降低的可能性是对照组的5倍（比值比，5.7；95%置信区间，2.1 - 15.7）。较年轻的病例（< 65岁）和吸烟者比对照组更有可能出现DRC降低。这些发现表明，DRC降低的个体患肺癌的风险增加。
