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谷胱甘肽转硫酶M1和T1基因型与食管癌危险性 病例

林东昕1 唐永明2 陆士新1 Fred F.Kadlubar2

  摘要 为探讨参与致癌物代谢的谷胱甘肽转硫酶(GST)M1和T1基因多型性与食管癌危险性的关系,以病例-对照分子流行病学方法,分析食管癌高发区河南林县的食管癌、食管上皮重度增生病例和性别、年龄配对的正常对照者(各45例)的GSTM1和GSTT1基因型分布的差异。基因组DNA来自研究对象的食管外科手术标本或细胞学检查获得的食管上皮细胞,以多重聚合酶链反应方法进行基因分型。结果:食管癌、食管上皮重度增生病例和正常对照组GSTM1基因缺失率分别为44.4%、44.4%和46.7%;GSTT1基因缺失率分别为40.0%、37.8%和51.1%,差别均无显著性。然而,正常对照者中既是GSTM1阳性又是GSTT1阳性的基因型比例(22.2%)显著低于食管癌病例(40.0%)和食管上皮重度增生病例(37.8%),比值比(95%可信限)分别为4.20(1.23~14.36)和2.64(0.84~8.30)。结果提示,GSTM1或GSTT1基因多型性单独似乎与食管癌危险性无关,但两者的阳性基因型联合可能是食管癌的危险性因素。
  关键词 食管癌 谷胱甘肽转硫酶 基因多型性 分子流行病学
Glutathione S-Transferase M1, T1 Genotypes and the Risk of Esophageal Cancer: A Case-Control Study Lin Dongxin*, Tang Yongming, Lu Shixin, et al.*Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021
  Abstract To examine the association between genetic polymorphisms of glutathione S-transferase (GST) M1 and T1 and susceptibility to esophageal cancer, a multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from surgically removed esophageal tissues or scraped esophageal cells from cases with cancer (n=45), cases with severe hyperplasia (n=45), and sex/age matched normal controls (n=45) from a high-risk area, Linxian, China. Results showed that the frequency of the GSTM1-null genotype in cancer cases (44.4%) or hyperplasia cases (44.4%) was not significantly different from that in controls (46.7%). Similarly, no statistically significant differences were observed in the frequency of GSTT1-null genotype in cancer cases (40.0%) or hyperplasia cases (37.8%) when compared with the controlled population (51.1%). However, the frequency of combined GSTM1-nonnull and GSTT1-nonnull genotypes in cases with cancer (40.0%) and cases with hyperplasia (37.8%) showed a significant increase compared to that in controls (22.2%). Persons with both GSTM1 and GSTT1 positive genotypes had 4-f

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