Reduced DNA repair capacity in lung cancer patients.
Reduced DNA repair capacity in lung cancer patients.
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DOI：
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发表时间：
1996-09
期刊：
影响因子：
11.2
通讯作者：
Q. Wei;Lie Cheng;W. Hong;M. Spitz
中科院分区：
文献类型：
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作者：
Q. Wei;Lie Cheng;W. Hong;M. Spitz
尽管肺癌是烟草诱发的恶性肿瘤的典型，但宿主特异性因素会调节对烟草致癌的易感性。 DNA 修复的变化可能会影响 DNA 损伤的去除率和突变的固定率。为了检验基因决定的 DNA 修复能力 (DRC) 调节肺癌易感性的假设，我们对 51 名新诊断且既往未接受治疗的肺癌患者和 56 名从当地社区中心确定的对照进行了试点病例对照研究，其频率与病例的年龄、性别和种族相匹配。对受试者进行确定和访谈，以进行正在进行的肺癌易感性分子流行病学调查。我们使用宿主细胞再激活测定来测量受试者外周血淋巴细胞中的 DRC，该测定测量因暴露于 75 microM 苯并（a）芘二醇环氧化物而受损的报告基因的细胞再激活。病例中 DRC 的平均水平 (3.3%) 显着低于对照组 (5.1%) (P < 0.01)。只有 9 例 (18%) 的 DNA 修复水平高于对照组的修复中值。对照中 DRC 的中位水平用作计算比值比的截止值。调整年龄、性别、种族和吸烟状况后，病例 DRC 降低的可能性是对照组的五倍（比值比，5.7；95% 置信区间，2.1-15.7）。与对照组相比，年轻病例（< 65 岁）和吸烟者更有可能降低 DRC。这些发现表明，DRC 降低的个体患肺癌的风险增加。
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.