Jeon Hyo-Sung, Kim Kyung Mee, Park Sun Ha, Lee Su Yeon, Choi Jin Eun, Lee Ga Young, Kam Sin, Park Rang Woon, Kim In-San, Kim Chang Ho, Jung Tae Hoon, Park Jae Yong
Cancer Research Institute, School of Medicine, Kyungpook National University, Dong In 2 Ga 101, Daegu, 700-422, Korea.
Carcinogenesis. 2003 Oct;24(10):1677-81. doi: 10.1093/carcin/bgg120. Epub 2003 Jul 17.
DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.
DNA修复在保护基因组免受致癌因素（如烟草烟雾中的致癌因素）的损伤方面起着关键作用。因此，DNA修复能力降低会增加患吸烟相关癌症的易感性。最近，在着色性干皮病G组（XPG）基因中发现了几种多态性，这些多态性可能会影响DNA修复能力，从而调节癌症易感性。我们研究了XPG基因中His1104Asp多态性与肺癌风险之间的关系。研究人群包括310例肺癌患者和311例健康对照，他们在年龄和性别上进行了频率匹配（1:1）。Asp/Asp基因型在对照组（28.9%）中比在病例组（18.7%）中更常见，当将His/His和His/Asp基因型合并作为参考时，与肺癌风险显著降低相关[调整后的优势比（OR）=0.54，95%置信区间（CI）=0.37-0.80]。在分层分析中，Asp/Asp基因型对肺癌的保护作用在老年受试者（调整后的OR = 0.51，95% CI = 0.37-0.80）、男性（调整后的OR = 0.54，95% CI = 0.35-0.83）和轻度吸烟者（调整后的OR = 0.48，95% CI = 0.25-0.94）中具有统计学意义。当按组织学类型分析肺癌时，Asp/Asp基因型与鳞状细胞癌风险显著降低相关（调整后的OR = 0.55，95% CI = 0.34-0.88）和小细胞肺癌（调整后的OR = 0.44，95% CI = 0.20-0.97），但腺癌风险降低不显著（调整后的OR = 0.64，95% CI = 0.36-1.12）。这些结果表明，XPG密码子1104多态性与肺癌的遗传易感性有关。
