Chizhikov V V, Gaspar'ian A V, Zborovskaia I B
Institute of Carcinogenesis, Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia.
Genetika. 2001 Oct;37(10):1388-95.
PCR-based typing of Hras1 minisatellite alleles was carried out in 226 non-small cell lung cancer (NSCLC) patients and 207 unaffected controls. Application of this method permitted detection of four common (a1 to a4) and 25 other alleles, differing from any common allele by one or more repeat units. Depending on their frequency in control group, these alleles were defined as intermediate or rare (the frequency over 0.5% or less than 0.5%, respectively). It was established that the frequency of rare alleles in the group of NSCLC patients (7.1%) was statistically significantly higher than in healthy individuals (2.2%, p = 0.002), while the difference in the distribution of common and intermediate alleles between the compared groups was not statistically significant. In addition, rare Hras1 alleles were more frequent (p = 0.02) among nonsmoking patients compared to the patients subjected to of tobacco carcinogens. The presence of "heavy" (a3-a4) alleles was associated with an increased risk of low-differentiated and/or actively metastasizing tumors and also with the risk of lung cancer in the patients under 50 years of age (p < 0.05). These data indicate that an approach including application of modern highly sensitive techniques of Hras1 allele typing in combination with preliminary examination of healthy control population can be employed for identifying carcinogenic risk groups as well as for prognosis of the NSCLC clinical course.
在226例非小细胞肺癌(NSCLC)患者和207例未受影响的对照者中进行了基于聚合酶链反应(PCR)的Hras1微卫星等位基因分型。应用该方法可检测到4种常见(a1至a4)等位基因和25种其他等位基因,这些等位基因与任何常见等位基因在一个或多个重复单元上存在差异。根据它们在对照组中的频率,这些等位基因被定义为中等频率或罕见频率(频率分别超过0.5%或低于0.5%)。结果表明,NSCLC患者组中罕见等位基因的频率(7.1%)在统计学上显著高于健康个体(2.2%,p = 0.002),而比较组之间常见和中等频率等位基因的分布差异无统计学意义。此外,与接触烟草致癌物的患者相比,非吸烟患者中罕见的Hras1等位基因更为常见(p = 0.02)。“重”(a3 - a4)等位基因的存在与低分化和/或活跃转移肿瘤的风险增加相关,也与50岁以下患者患肺癌的风险相关(p < 0.05)。这些数据表明,一种包括应用现代高灵敏度Hras1等位基因分型技术并结合对健康对照人群进行初步检查的方法,可用于识别致癌风险组以及预测NSCLC的临床病程。