p21和p27基因多态性与女性肺癌的关联研究

Study on the correlation between polymorphisms of p21 and p27 genes and the genetic susceptibility of non-small cell lung carcinoma in women

目的探讨p21和p27基因多态性与女性非小细胞肺癌(NSCLC)遗传易感性的关系。方法应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法,分析110例女性NSCLC患者和124例女性健康对照人群p21基因3'非翻译区(3'UTR)和p27基因第109密码子多态性位点的基因型。结果p21基因突变型(C/T+T/T)频率在病例组(76.4%)显著高于对照组(56.5%)[(χ2=10.27,P=0.001)。携带T等位基因(C/T和T/T基因型)能显著增加这一人群NSCLC发病风险(经年龄校正的OR=2.60,95%CI(1.46,4.61)]。根据吸烟状况和年龄分层分析发现,p21基因突变型(C/T+T/T)频率在不吸烟病例组(86.0%)和≥50岁病例组(76.6%)均显著高于对照组(P<0.01),携带C/T和T/T基因型可显著增高不吸烟者和50岁以上人群的NSCLC发病风险[经年龄校正的OR分别为4.95和2.68,95%CI分别为(2.36,10.40)和(1.41,5.08)]。p27等位基因和基因型总体分布在2组差异无统计学意义(P>0.05),分层分析也未显示出结果有差异性。对淋巴结转移的研究显示p21和p27基因多态性与NSCLC患者的淋巴结转移无关。结论p21基因3'UTR多态性与该女性人群NSCLC发病风险有关,C/T、T/T基因型可能增加NSCLC发病风险,尤其对于不吸烟个体及50岁以上者其可能是NSCLC的发病危险因素。p27基因多态性与该女性人群NSCLC遗传易感性无关。p21和p27基因多态性与NSCLC患者淋巴结转移无关。

Objective To investigate the correlation between polymorphisms of p21 and p27 genes and the genetic susceptibility of non-small cell lung carcinoma （ NSCLC ） in women. Methods The single nucleotide polymorphisms（ SNPs）in the 3＇-untranslated region of p21 gene and in codon 109 of p27 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）in 110 NSCLC patients and 124 healthy subjects. Results The frequency of the p21 gene 3＇ UTR mutant genotypes （ C/T ＋ T/T ） in NSCLC patients （76.4%）was significantly higher than that in healthy subjects（56.5%, P 〈 0.01 ）. As compared with the C/C genotype,the genotypes with the 3＇UTR T allele（ C/T ＋ T/T）significantly increased the susceptibility to NSCLC （ age adjusted OR ： 2.60,95 % CI = 1.46 - 4.61 ）. When stratified for smoking and aging, the frequency of combination of C/T and T/T genotype in non-smoking patients（ 86.0% ）and in patients whose age was above 50 years（76.6% ）were significantly higher than that in controls. The C/T and T/T genotype significantly increased the risk of pathogenesis of NSCLC in non-smokers （adjusted OR = 4.95,95% CI=2.36 - 10.40）and in group that patients＇ age was above 50 years （ adjusted OR = 2.68,95 % CI = 1.41 - 5.08 ）. There was no significant difference in overall genotype and allelotype distribution of the p27 gene variants between patients and controls, and nor did when stratified analyzing. There was no correlation between the lymph node metastasis and the two gene polymorphisms. Conclusion The research results suggest that in this population, the p21 gene 3＇ UTR polymorphism is associated with NSCLC, C/T and T/T genotype may increase the risk of NSCLC, especially in nonsmokers and individuals whose age is above 50 years. The p27 gene V109G polymorphism may not be associated with the susceptibility of NSCLC. There is no correlation between the lymph node metastasis and the two gene polymorphisms.