Sikdar Nilabja, Paul Ranjan Rashmi, Roy Bidyut
Anthropology and Human Genetics Unit, Biological Sciences Division, Indian Statistical Institute, Kolkata, India.
Int J Cancer. 2004 Mar;109(1):95-101. doi: 10.1002/ijc.11610.
Polymorphism in glutathione S-transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0-2.0) and lower (OR = 1.4; 95% CI = 1.0-1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0-4.0; OR = 2.0, 95% CI = 1.0-4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0-9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0-5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals.
谷胱甘肽S-转移酶（GST）基因的多态性会导致酶活性的变化，可能会影响吸烟者和/或无烟烟草使用者患口腔癌和白斑病的易感性。在这项病例对照研究中，包括109名白斑病患者、256名口腔癌患者和259名对照，通过聚合酶链反应-限制性片段长度多态性方法确定了GSTM1、GSTT1、GSTM3和GSTP1基因座的基因型频率，并通过多因素逻辑回归分析来确定疾病风险。当对所有个体进行比较时，患者和对照中GSTM1、GSTM3和GSTT1基因型的分布没有显著差异。相比之下，与对照相比，口腔癌患者中GSTP1第105密码子的ile/ile基因型频率显著更高（OR = 1.5；95% CI = 1.0 - 2.0），而val-ala单倍型变异频率显著更低（OR = 1.4；95% CI = 1.0 - 1.9）。还对具有不同烟草习惯和剂量的患者中所有基因型对口腔癌和白斑病风险的影响进行了分析。携带GSTM3（A/A）基因型的吸烟者患癌和患白斑病的风险增加（OR分别为2.0，95% CI = 1.0 - 4.0；OR为2.0，95% CI = 1.0 - 4.4）。因此，GSTM3（A/A）基因型可能成为了解哪些白斑病会转化为癌症的标志物之一。重度嚼烟（> 124嚼烟年）会增加携带GSTT1纯合无效基因型个体患癌的风险（OR = 3.0；95% CI = 1.0 - 9.8）。此外，终生吸烟暴露增加（> 11.5包年）会增加携带GSTM1纯合无效基因型个体患白斑病的风险（OR = 2.4；95% CI = 1.0 - 5.7）。可能提示GSTP1、GSTM1、GSTM3和GSTT1基因的多态性在不同烟草习惯人群中对癌症和白斑病风险的调节作用存在差异。
