Sharma Neha, Singh Amrita, Singh Navneet, Behera Digamber, Sharma Siddharth
Department of Biotechnology, Thapar University, Patiala, Punjab 147002, India.
Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Sector 14, Chandigarh, India.
Cancer Epidemiol. 2015 Dec;39(6):947-55. doi: 10.1016/j.canep.2015.10.014. Epub 2015 Nov 9.
A number of studies done so far in different populations have shown that polymorphisms within the GST genes play an important role in determining individual susceptibility to lung cancer; however, data obtained so far have been contradictory within the same or different populations. Few studies have focused on the combinatorial effect of the GST genes on susceptibility to lung cancer and also for different histological subtypes. Our aim is to investigate the roles of GSTM1, GSTT1, and GSTP1 polymorphisms as genetic modifiers of risk for lung cancer and histological subtypes using a larger sample size in a North Indian population.
In total 540 subjects (270 lung cancer cases and 270 controls) were evaluated for the GST polymorphism. Genotyping for the GSTM1, GSTT1 and GSTP1 gene was done by using a multiplex PCR and PCR-RFLP method.
GSTM1 null genotype was found to be associated with lung cancer (OR=1.65, 95%CI: 116-2.3, P=0.005) and this risk was higher in cases of adenocarcinoma (ADCC). GSTT1 and GSTP1 did not show any significant association with lung cancer; however, when stratified for histological subtypes a significant association was observed for ADCC and small-cell lung cancer (SCLC) for both GSTT1 null and variant GSTP1 genotypes. The combined 'at risk' genotypes of null GSTM1 and GSTT1 genes were found to be associated with lung cancer risk, and this risk was higher in cases of ADCC (OR=4.09, 95%CI: 110-10.2, P=0.002). There is a twofold increased risk for lung cancer with the null GSTM1 and wild-type GSTP1 genotypes (P=0.0004); similarly, a fourfold increased risk was observed with the null GSTT1 and wild-type GSTP1 genotypes (P=0.0001).
The deficient GST genotypes seem thus to be important risk modifiers for lung cancer and related histological subtypes, especially in combination.
迄今为止，在不同人群中进行的多项研究表明，谷胱甘肽S-转移酶（GST）基因内的多态性在决定个体对肺癌的易感性方面起着重要作用；然而，迄今为止在同一或不同人群中获得的数据相互矛盾。很少有研究关注GST基因对肺癌易感性的联合作用，以及对不同组织学亚型的影响。我们的目的是在北印度人群中使用更大的样本量，研究GSTM1、GSTT1和GSTP1基因多态性作为肺癌及组织学亚型风险的遗传修饰因子的作用。
对总共540名受试者（270例肺癌患者和270名对照）进行GST多态性评估。采用多重聚合酶链反应（PCR）和PCR-限制性片段长度多态性（RFLP）方法对GSTM1、GSTT1和GSTP1基因进行基因分型。
发现GSTM1无效基因型与肺癌相关（比值比[OR]=1.65，95%置信区间[CI]：1.16-2.3，P=0.005），腺癌（ADCC）患者的这种风险更高。GSTT1和GSTP1与肺癌未显示出任何显著关联；然而，按组织学亚型分层时，GSTT1无效基因型和GSTP1变异基因型与ADCC和小细胞肺癌（SCLC）均存在显著关联。发现GSTM1和GSTT1无效基因的联合“风险”基因型与肺癌风险相关，ADCC患者的这种风险更高（OR=4.09，95%CI：1.10-10.2，P=0.002）。GSTM1无效基因型和野生型GSTP1基因型使肺癌风险增加两倍（P=0.0004）；同样，GSTT1无效基因型和野生型GSTP1基因型使肺癌风险增加四倍（P=0.0001）。
因此，缺陷型GST基因型似乎是肺癌及相关组织学亚型的重要风险修饰因子，尤其是联合存在时。
