Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population
Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population
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中国人群细胞周期基因的潜在功能多态性与非小细胞肺癌的生存
DOI：
10.1016/j.lungcan.2010.11.001
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发表时间：
2011-07-01
期刊：
影响因子：
5.3
通讯作者：
Shu, Yongqian
中科院分区：
文献类型：
--
作者：
Ma, Hongxia;Chen, Jiaping;Shu, Yongqian
细胞周期控制着细胞的增殖和生长，并受到包括细胞周期蛋白、CDK和CKI在内的一些调节因子的严格控制。在包括非小细胞肺癌（NSCLC）在内的一组癌症中经常观察到细胞周期基因的生殖系和体细胞突变。在这项研究中，我们假设细胞周期基因中潜在的功能性单核苷酸多态性（SNP）可能有助于中国NSCLC的预后。关键细胞周期基因的54个潜在功能多态性（CDK1、CDK2、CDK4、CDK6、CDK7、CCND1、CCND2、CCND3、CCNE1、CCNA1、CCNA2、CCNB1、CCNH、p15、p16、p18、p19、p21、p27、Cdc 25 A和Cdc 25 B）通过使用Illumina SNP基因分型平台进行基因分型，以评估它们与568名患者的临床队列中的NSCLC生存的相关性。我们发现p18 rs3176447变异基因型与NSCLC患者死亡风险的降低显著相关（相加模型中校正的HR = 0.74，95% CI = 0.57-0.97;显性模型中校正的HR = 0.76，95% CI = 0.55-0.97）;然而，p21 rs 2395655变异基因型与死亡风险的增加显著相关，（相加模型中校正HR = 1.21，95% CI = 1.02-1.42;隐性模型中校正HR = 1.38，95% CI = 1.07-1.78）。此外，这两个SNP的不利基因型的组合效应在患有鳞状细胞癌、晚期和没有化疗或放疗的患者中更为突出。虽然确切的生物学功能仍有待探讨，我们的研究结果表明，p18和p21的多态性与中国人群的非小细胞肺癌的预后可能有关联。需要进一步的大型和功能性研究来证实我们的发现。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The cell cycle governs the proliferation and growth of cells and is strictly controlled by some regulators including cyclins, CDKs and CKIs. Germ-line and somatic mutations in cell cycle genes were frequently observed in a subset of cancers including non-small cell lung cancer (NSCLC). In this study, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in cell cycle genes may contribute to the prognosis of NSCLC in China. 54 potentially functional polymorphisms in key cell cycle genes (CDK1, CDK2, CDK4, CDK6, CDK7, CCND1, CCND2, CCND3, CCNE1, CCNA1, CCNA2, CCNB1, CCNH, p15, p16, p18, p19, p21, p27, Cdc25A and Cdc25B) were genotyped by using Illumina SNP genotyping platform to evaluate their associations with survival of NSCLC in a clinical cohort of 568 patients. We found that p18 rs3176447 variant genotypes were significantly associated with the decreased risk of death of NSCLC patients (adjusted HR = 0.74, 95% CI = 0.57-0.97 in an additive model; adjusted HR = 0.76, 95% CI = 0.55-0.97 in a dominant model); however, p21 rs2395655 variant genotypes were significantly associated with the increased risk of death (adjusted HR = 1.21, 95% CI = 1.02-1.42 in an additive model; adjusted HR = 1.38, 95% CI = 1.07-1.78 in a recessive model). Furthermore, the combined effect of unfavorable genotypes for these two SNPs was more prominent in patients with squamous cell carcinoma, late stage and without chemo- or radio-therapy. Although the exact biological function remains to be explored, our findings suggest possible association of polymorphisms of p18 and p21 with the prognosis of NSCLC in a Chinese population. Further large and functional studies are needed to confirm our findings. (C) 2010 Elsevier Ireland Ltd. All rights reserved.