p73 G4C14-to-A4T14 polymorphism and risk of lung cancer
p73 G4C14-to-A4T14 polymorphism and risk of lung cancer
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DOI：
10.1158/0008-5472.can-04-1804
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发表时间：
2004-10-01
期刊：
影响因子：
11.2
通讯作者：
Wei, QY
中科院分区：
文献类型：
--
作者：
Li, GJ;Wang, LE;Wei, QY
控制细胞过程如细胞周期、DNA修复和细胞凋亡的基因中的遗传变异可能调节肺癌风险。p73具有某些p53样活性，并在调节这些过程中起重要作用。p73基因第2外显子的非编码区存在两个完全连锁不平衡的多态性，这两个多态性可能改变p73蛋白的翻译效率。为了验证p73基因多态性在肺癌病因中发挥作用的假设，我们对1054例新诊断的肺癌患者和1139例无癌对照进行了一项以医院为基础的病例对照研究，并评估了p73变异AT等位基因与肺癌风险之间的关系。无癌症对照组的频率与年龄（5岁）、性别和吸烟状况的病例相匹配，所有受试者均为非西班牙裔白人。AT等位基因和基因型变异在病例组中的发生率高于对照组（P = 0.0007和P < 0.001）。与GC/GC基因型相比，变异的GC/AT和AT/AT基因型与肺癌的风险显著增加[校正比值比（OR）分别为1.32，95%CI为1.10-1.59和1.54，95%CI为1.05-2.26]，呈等位基因剂量效应关系（趋势检验：P < 0.001）。AT等位基因（GC/AT+AT/AT）相关的风险在年轻（550岁）个体（OR = 1.53，95%CI，1.00-2.37）、男性（OR = 1.61，95%CI，1.26-2.06）、轻度吸烟者（OR = 1.58，95%CI，1.17-2.14）和鳞状细胞肺癌（OR = 1.79，95%CI，1.32-2.42）中更为明显。这些结果表明，这种p73基因多态性可能是一个标记的易感性肺癌。
Genetic variants in genes controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate lung cancer risk. p73 has some p53-like activity and plays an important role in modulating these processes. The noncoding region of exon 2 of the p73 gene has two polymorphisms that are in complete linkage disequilibrium with one another, which may alter translation efficiency of the p73 protein. To test the hypothesis that this p73 polymorphism plays a role in the etiology of lung cancer, we conducted a hospital-based case-control study of 1054 patients newly diagnosed with lung cancer and 1139 cancer-free controls and evaluated the association between the p73 variant AT allele and risk of lung cancer. Cancer-free controls were frequency matched to the cases by age ( 5 years), sex, and smoking status, and all subjects were non-Hispanic whites. The variant AT allele and genotypes were more common among the cases than among the controls (P = 0.0007 and P < 0.001, respectively). Compared with the GC/GC genotype, the variant GC/AT and AT/AT genotypes were associated with a statistically significantly increased risk for lung cancer [adjusted odds ratio (OR) = 1.32, 95% confidence interval (Cl), 1.10-1.59 and OR = 1.54, 95% CI, 1.05-2.26, respectively] in an allele dose-effect relationship (trend test: P < 0.001). The risk associated with the AT allele (GC/AT+AT/AT) was more pronounced in younger (:550 years) individuals (OR = 1.53, 95% Cl, 1.00-2.37), men (OR = 1.61, 95% Cl, 1.26-2.06), light smokers (OR = 1.58, 95% Cl, 1.17-2.14), and squamous cell lung carcinoma (OR = 1.79, 95% CI, 1.32-2.42). These results suggest that this p73 polymorphism may be a marker for susceptibility to lung cancer.