KRAS基因多态性与云南汉族人群非小细胞肺癌的相关性分析

  目的   探讨KRAS基因多态性与云南汉族人群非小细胞肺癌发生发展及病理类型的相关性。  方法   选取455例非小细胞肺癌患者，391例健康对照作为研究对象。采用Taqman探针基因分型法对KRAS基因3’UTR区域3个单核苷酸多态性（single nucleotide polymorphism，SNP）位点rs12587（G > T） 、rs12245（A > C）、 rs1137282（A > G）进行基因分型。根据分型结果，分析等位基因、基因型及单倍型与非小细胞肺癌发生、病理类型（鳞癌、腺癌）和临床分期（I+II期、III+IV期）的相关性。  结果   rs12587（G > T）位点等位基因G在非小细胞肺癌组的分布频率显著高于对照组（P = 0.008，OR = 1.365，95%CI 1.086～1.716）；在显性模式下携带T等位基因的个体（G/T+T/T）患非小细胞肺癌的风险显著降低（P = 0.011，OR = 0.70 ，95%CI 0.53～0.92）。病例分层分析发现，鳞癌组与对照组的rs12587（G > T）位点等位基因和基因型频率，差异有统计学意义（P < 0.001、P = 0.001）；在显性模式下携带T等位基因的个体（G/T+T/T）患肺鳞癌的风险显著降低（P < 0.001，OR = 0.45 ，95%CI 0.30～0.68）。非小细胞肺癌病例组与对照组rs12245（A > C）位点等位基因分布频率及基因型，差异无统计学意义（P > 0.05）；在显性模式下携带A等位基因的个体（A/T+A/A）患非小细胞肺癌的风险显著降低（P = 0.028，OR = 0.73 ，95%CI 0.55～0.97）。病例分层分析发现鳞癌组与对照组的rs12245（A > C）位点等位基因和基因型频率，差异有统计学意义（P = 0.003、P = 0.001）；在超显性模式下，基因型为A/T的个体患肺鳞癌的风险显著降低（P<0.001，OR = 0.43 ，95%CI 0.28～0.67）。  结论  KRAS基因3’UTR区域SNP位点rs12587（G > T）等位基因G可能是云南汉族人群非小细胞肺癌及鳞癌发生的风险因素。SNP位点rs12245（A > C）等位基因A可能是云南汉族人群非小细胞肺癌发生的保护性因素。

Correlation between KRAS Gene Polymorphism and Non-small Cell Lung Cancer in Yunnan Han Population

  Objective   To investigate the correlation between KRAS gene polymorphism and the occurrence and development of non-small cell lung cancer in Yunnan Han population.   Methods   In this study, 455 patients with non-small cell lung cancer and 391 healthy controls were selected as the research objects. Three single nucleotide polymorphism （SNP） sites rs12587 （G > T）, rs12245 （A > C）, rs1137282 （A > G） in the 3′UTR region of KRAS gene were identified by Taqman probe genotyping. According to the typing results, the correlations of alleles, genotypes and haplotypes with the occurrence, pathological types （squamous cell carcinoma, adenocarcinoma） and clinical stages （I+II, III+IV） of non-small cell lung cancer were analyzed.   Results   The distribution frequency of rs12587 （G > T） allele G in the non-small cell lung cancer group was significantly higher than that in the control group （P = 0.008, OR = 1.365, 95%CI 1.086～1.716）. It was carried in the dominant mode Individuals with the T allele （G/T+T/T） had a significantly lower risk of developing non-small cell lung cancer （P = 0.011, OR = 0.70, 95%CI 0.53～0.92）. Case stratification analysis found that the allele and genotype frequencies of the rs12587 （G > T） locus were significantly different between the squamous cell carcinoma group and the control group （P < 0.001, P = 0.001）; Individuals with the T allele （G/T+T/T） had a significantly lower risk of lung squamous cell carcinoma （P < 0.001, OR = 0.45, 95%CI 0.30～0.68）. There was no significant difference in the distribution frequency of the rs12245 （A > C） locus allele and genotype between the non-small cell lung cancer case group and the control group （P > 0.05）; Individuals （A/T+A/A） had a significantly lower risk of developing non-small cell lung cancer （P = 0.028, OR = 0.73, 95%CI 0.55～0.97）. Case stratification analysis found that the allele and genotype frequencies of the rs12245 （A > C） locus were significantly different between the squamous cell carcinoma group and the control group （P = 0.003, P = 0.001）; Individuals with genotype A/T had a significantly lower risk of lung squamous cell carcinoma （P < 0.001, OR = 0.43, 95%CI 0.28～0.67）.   Conclusions   The G allele of the SNP site rs12587 （G > T） in the 3′UTR region of KRAS gene may be a risk factor for the occurrence of non-small cell lung cancer and squamous cell carcinoma in Yunnan Han population. SNP rs12245 （A > C） allele A may be a protective factor for the occurrence of non-small cell lung cancer in Yunnan Han population.