Lindstedt B A, Ryberg D, Zienolddiny S, Khan H, Haugen A
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Anticancer Res. 1999 Nov-Dec;19(6C):5523-7.
To further evaluate lung cancer risk associated with rare Hras1 VNTR alleles and possible biological mechanisms.
The Hras1 VNTR was genotyped in 295 lung cancer patients and 500 healthy controls by PCR and high resolution electrophoresis. Microsatellite alterations were examined in 168 tumors by PCR and capillary electrophoresis.
35 Hras1 VNTR alleles were found, of which 24 were defined as rare. A relative risk of 3.3 (95% CI; 1.9-6.0) associated with rare alleles was obtained using the total groups. Increased risk was significant both for males and females. When a matched control group was used, a relative risk of 12.7 (95% CI; 1.7-93.9) was calculated for individuals with rare alleles at the Hras1 VNTR locus. A low frequency of microsatellite alterations was observed (4.7%) in lung tumors. The frequency of altered microsatellite loci was higher among patients with rare Hras1 VNTR alleles than among patients with common alleles.
Rare Hras1 VNTR alleles are associated with lung cancer risk, and a genetic mechanism which increases allelic diversity may be involved.
进一步评估与罕见的Hras1可变数目串联重复序列（VNTR）等位基因相关的肺癌风险及可能的生物学机制。
采用聚合酶链反应（PCR）和高分辨率电泳对295例肺癌患者和500例健康对照者的Hras1 VNTR进行基因分型。通过PCR和毛细管电泳对168个肿瘤的微卫星改变进行检测。
共发现35个Hras1 VNTR等位基因，其中24个被定义为罕见等位基因。在全部研究对象中，罕见等位基因相关的相对风险为3.3（95%可信区间[CI]：1.9 - 6.0）。男性和女性的风险增加均具有显著性。当使用匹配对照组时，Hras1 VNTR位点具有罕见等位基因的个体的相对风险为12.7（95% CI：1.7 - 93.9）。在肺肿瘤中观察到微卫星改变的频率较低（4.7%）。具有罕见Hras1 VNTR等位基因的患者中微卫星位点改变的频率高于具有常见等位基因的患者。
罕见的Hras1 VNTR等位基因与肺癌风险相关，可能涉及增加等位基因多样性的遗传机制。
