【作者】 李作生； 李保庆； 张云杰； 张月峰； 马玉泉；

【Author】 Li Zuo-Sheng Li Bao-Qing Zhang Yun-Jie et al. Department of Thoracic Surgery, The Fourth Hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院胸外科；

【摘要】 目的:探讨p21外显子3的3,非翻译区(3,-UTR) 第20碱基对的单核苷酸多态性(SNP)和p27基因V109G 多态性与中国北方人非小细胞肺癌遗传易感性及淋巴结转移的关系。方法:采用聚合酶链反应-限制性片段长度多态性分析方法,分析中国北方202名非小细胞肺癌患者和265 名健康对照者p21基因3,UTR和p27基因第109密码子 SNP位点的基因型。结果:p21和p27基因型在NSCLC病例组和健康对照组的分布均符合Hardy-Weinberg平衡(P >0．05)。p21基因突变型(C／T+T／T)频率在肺癌患者组 (72．8％)显著高于健康对照组(63．8％)(x2=4．242,P=0． 039)。与C／C基因型相比,携带T／T和C／T基因型可显著增加这一人群非小细胞肺癌发病风险(经性别,年龄校正的OR=1．54,95％CI=1．03—2．30)。根据吸烟状况分层分析发现,不吸烟患者组p21基因T等位基因频率(49．3％)显著高于不吸烟健康对照组(38．0％)(x2=4．810,P=0． 028)。p21基因突变型(C／T+T／T)频率在不吸烟肺癌患者组(81．6％)显著高于不吸烟健康对照组(62．5％)(x2 =7．880,P=0．005)。与C／C基因型相比,携带C／T和T／ T基因型可显著增高不吸烟者的非小细胞肺癌发病风险(经性别,年龄校正的OR值为2．78,95％CI=1．38—5．63)。按组织学类型分层分析发现,p21基因型及等位基因型在腺癌组及鳞癌组中的分布与健康对照组相比均无显著性差异。对性别进行的分层分析发现,在女性组, p21基因T／T型频率在病例组(19．6％)明显高于对照组(7．5％),C／C型频率在病例组(23．9％)则明显低于对照组(40．3％),两者相比有显著性差异(x2=5．398,P=0．020)。携带T／T基因型较之C／C型能显著增加女性人群NSCLC发病风险(经性别,年龄校正的OR=4．83,95％CI=1．26-18．62)。根据有无淋巴结转移进行的分层分析未发现p21基因型分布在有淋巴结转移组和无淋巴结转移组的差异(P>0．05)。p27基因等位基因频率和基因型总体分布在病例组和对照组无显著性差异(P>0．05),与T／T基因型相比,携带T／G和G／ G基因型并不增加这一人群非小细胞肺癌发病风险(经性别,年龄校正的OR=1．07,95％CI=0．49—2．33)。根据吸烟状况,病理类型及淋巴结转移情况进行的分层分析也未发现p27基因型分布在病例组与对照组有显著性差异(P>0． 05)。结论:1．p21基因3,-UTR SNP与NSCLC发病有关,C／T,T／T基因型可增加NSCLC发病风险,尤其对于不吸烟个体及女性其可能是肺癌的发病危险因素,而与病理类型及淋巴结转移无关。2．p27基因V109G多态性与中国北方人群NSCLC易感性及淋巴结转移无关。更多还原

【Abstract】 Objective: To investigate the correlation of the single nucleotide polymorphism (SNP) at the 20bp 3’-untranslated region (3’UTR) of p21 gene exon 3 and the 109th codon of p27 gene (V109G) for association with genetic susceptibility and lymph node metastasis of non-small cell lung carcinoma (NSCLC) in a North China population. Methods: Two hundred and two patients with histologi-cally confirmed non-small cell lung carcinoma and 265 cancer-free individuals were detected genotype of p21 and p27 gene SNPs by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The distribution of the p21 and p27 genotypes in both NSCLC patients and healthy controls were accorded with Hardy-Weinberg equilibrium (all P values are above 0.05). The Results showed that the frequency of the p21 gene 3’UTR mutant genotypes (C/T+T/T) in NSCLC patients (72.8%) was significantly higher than that in healthy controls (63.8%) (x2 = 4.24, P=0.039). Compared to the C/C genotype, the genotypes with the 3’UTR T allele (C/T +T/T) significantly increased the susceptibility to NSCLC (sex and age adjusted odds ratio, i.e. aOR was 1. 54,95%CI=1.03-2.30). Stratified analysis found that the p21 gene T allele frequency in non-smoking patients (49. 3 %) was significantly higher than that in healthy nonsmokers (38.0%) (x2=4.81, P=0.028). The frequency of C/T and T/T genotype in non-smoking patients (81.6%) was significantly higher than that in healthy nonsmokers (62.5%) (X2 = 7.88, P=0.005). Therefore, nonsmokers with the p21 C/T or T/T genotype significantly increased the risk to develop NSCLC (aOR=2.78, 95%CI=1.38-5.63). When stratified by pathological types, the frequency of the p21 genotype didn’ t significantly increased in patients with adenoearcinoma (AC) and squamous cell carcinoma (SC) than that in healthy controls. Another stratification is gender. In female, the frequency of T/T genotype in NSCLC patients (19.6%) was significantly higher than that in healthy controls (7.5%), whereas the frequency of C/C genotype(23.9%) was significantly lower than that in healthy controls (40.3%) (x2 = 5.40, P=0.020). Female group with the T/T genotype significantly increased the susceptibility to develop NSCLC, compared with female individuals who taking the C/C genotype (aOR=4.83, 95%CI=1.26-18.62). The NSCLC cases were further stratified according to the status of lymph node metastasis at the time of diagnosis. No significant difference was observed in the frequencies of the p21 genotypes between NSCLC patients with positive and negative lymph node (P>0.05). The overall genotype and allelotype distribution of the p27 gene variants in patients and controls was not significantly different (all P values are above 0.05), furthermore, there were not differences of the overall genotype and allelotype distribution between NSCLC patients and healthy controls when stratified by smoking status, pathological types, sex, and status of lymph node metastas更多还原