Eom Sang-Yong, Zhang Yan Wei, Kim Sung-Hoon, Choe Kang-Hyeon, Lee Kye Young, Park Jung-Duck, Hong Yun-Chul, Kim Yong-Dae, Kang Jong-Won, Kim Heon
Department of Preventive Medicine, College of Medicine, Chungbuk National University, 12 Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea.
Cancer Causes Control. 2009 Mar;20(2):137-45. doi: 10.1007/s10552-008-9225-7. Epub 2008 Sep 17.
We investigated the association of genetic polymorphisms of NQO1, ALDH2, CYP2E1, and the combined genotype of these genes on lung cancer risk, and also evaluated the association after stratification by cumulative smoking amounts and alcohol drinking levels.
The case-control study was performed in 387 lung cancer patients and 387 age- and sex-matched cancer-free controls. Direct interview was conducted and the genotypes of NQO1, ALDH2, and CYP2E1 were investigated using PCR-RFLP or 5'-nuclease activity assay.
The proportion of individuals with occupational history of mining was significantly higher in cases than in controls. The risk of lung cancer was significantly lower in light-drinkers (<108 g/week) than non-drinkers. The NQO1 Pro/Ser + Ser/Ser genotype showed an increased risk for lung cancer with a marginal significance (OR = 1.35, 95% CI = 0.99-1.86) compared with NQO1 Pro/Pro genotype. In heavy-smokers, the combination of NQO1 Pro/Ser + Ser/Ser and CYP2E1 c1/c1 genotype was associated with a significantly increased risk for lung cancer (OR = 2.25, 95% CI = 1.14-4.43) compared with those of NQO1 Pro/Pro and CYP2E1 c1/c2 + c2/c2 genotype. We found a significant interaction between alcohol drinking level and the CYP2E1 genotype (P = 0.0227).
Our result suggests that the risk of lung cancer is affected by smoking, alcohol drinking, and the genetic polymorphism of NQO1. In particular, genetic polymorphisms for NQO1, CYP2E1, and ALDH2 synergistically with cumulative smoking amounts and alcohol drinking levels interact in the carcinogenesis of lung cancer in Koreans.
我们研究了NQO1、ALDH2、CYP2E1基因多态性及其联合基因型与肺癌风险的关联，并通过累积吸烟量和饮酒水平分层评估了这种关联。
对387例肺癌患者和387例年龄及性别匹配的无癌对照进行了病例对照研究。进行直接访谈，并使用PCR-RFLP或5'-核酸酶活性测定法研究NQO1、ALDH2和CYP2E1的基因型。
有采矿职业史的个体比例在病例组中显著高于对照组。轻度饮酒者（<108克/周）患肺癌的风险显著低于不饮酒者。与NQO1 Pro/Pro基因型相比，NQO1 Pro/Ser + Ser/Ser基因型显示患肺癌的风险增加，具有边缘显著性（OR = 1.35，95% CI = 0.99 - 1.86）。在重度吸烟者中，与NQO1 Pro/Pro和CYP2E1 c1/c2 + c2/c2基因型相比，NQO1 Pro/Ser + Ser/Ser和CYP2E1 c1/c1基因型的组合与肺癌风险显著增加相关（OR = 2.25，95% CI = 1.14 - 4.43）。我们发现饮酒水平与CYP2E1基因型之间存在显著相互作用（P = 0.0227）。
我们的结果表明，肺癌风险受吸烟、饮酒和NQO1基因多态性影响。特别是，NQO1、CYP2E1和ALDH2基因多态性与累积吸烟量和饮酒水平在韩国人肺癌致癌过程中协同相互作用。
