Park Jung Min, Choi Jin Eun, Chae Myung Hwa, Lee Won Kee, Cha Sung Ick, Son Ji-Woong, Kim Chang Ho, Kam Sin, Kang Young Mo, Jung Tae Hoon, Park Jae Yong
Cancer Research Institute, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, 700-422, South Korea.
BMC Cancer. 2006 Mar 17;6:70. doi: 10.1186/1471-2407-6-70.
Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population.
The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.
The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46-0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39-0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33-0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37-0.87, P = 0.01, respectively).
These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.
环氧化酶-2(COX-2)在肺癌发生发展中起重要作用。COX-2基因的DNA序列变异可能导致COX-2产生和/或活性改变,进而引起个体间肺癌易感性的差异。为验证这一假说,我们在韩国人群中研究了COX-2基因3'-非翻译区8473T>C多态性与肺癌风险的关联。
采用基于聚合酶链反应(PCR)的引物引入限制性分析方法,对582例肺癌患者和582例年龄及性别频率匹配的健康对照者进行COX-2基因分型。
总体肺癌病例与对照组之间,COX-2 8473T>C基因型分布无显著差异。然而,按肿瘤组织学类型对病例进行分类时,与8473 TT基因型相比,8473 TC + CC基因型组合与腺癌风险显著降低相关(校正比值比=0.64;95%置信区间=0.46 - 0.90,P = 0.01)。分层分析显示,8473 TC + CC基因型组合对腺癌的保护作用在男性、年长者和曾经吸烟者中具有统计学意义(校正比值比分别为0.59;95%置信区间=0.39 - 0.91,P = 0.02;校正比值比=0.55;95%置信区间=0.33 - 0.93,P = 0.03;校正比值比=0.57;95%置信区间=0.37 - 0.87,P = 0.01)。
这些发现提示,COX-2 8473T>C多态性可作为肺腺癌遗传易感性的一个标志物。