Pandey S N, Jain M, Nigam P, Choudhuri G, Mittal B
Department of Gastroenterology, Sanjay Gandhi Post Institute of Medical Science, Lucknow - 226014, India.
Biomarkers. 2006 May-Jun;11(3):250-61. doi: 10.1080/13547500600648697.
The glutathione S-transferase (GSTs) are polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous potential carcinogens. Several allelic variants of polymorphic GSTs show impaired enzyme activity and are suspected to increase the susceptibility to various cancers. To find out the association of GST variants with risk of gallbladder cancer, the distribution of polymorphisms in the GST family of genes (GSTT1, GSTM1, GSTP1, and GSTM3) were studied in 106 cancer patients and 201 healthy controls. Genotypes were analysed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). The frequencies of GSTM1 null and GSTM3*BB genotypes did not differ between patients and controls. The overall frequency of GSTT1 null was lower in cases as compared with controls (p=0.003, Odds ratio (OR) = 0.2, 95% confidence interval (CI), 0.1-0.6). After sex stratification, the GSTT1 null frequency was reduced only in female patients (p=0.008, OR = 0.2, 95% CI = 0.1-0.6). However, the GSTP1, ile/val genotype and the val allele were significantly higher in cases than controls (p=0.013, OR = 1.9, 95% CI = 1.1-3.1; p=0.027, OR = 1.5, 95% CI = 1.0-2.1), respectively. To study gene-gene interactions, a combined risk of gallbladder cancer due to ile/val or val/val were calculated in combination with null alleles of GSTM1 and GSTT1 or the *B allele of GSTM3, but there was no enhancement of risk. Gallstones were present in 57.5% of patients with gallbladder cancer, but there were no significant differences between allelic/genotype frequencies of the studied GST genes polymorphisms between patients with or without gallstones. To best of our knowledge, this is the first paper showing ile/val genotypes and val allele of GSTP1 to be associated with higher risk of gallbladder cancer.
谷胱甘肽S-转移酶（GSTs）是一个多态性的解毒酶超基因家族，参与多种潜在致癌物的代谢。多态性GSTs的几个等位基因变体显示酶活性受损，并被怀疑会增加对各种癌症的易感性。为了找出GST变体与胆囊癌风险之间的关联，我们在106名癌症患者和201名健康对照中研究了GST基因家族（GSTT1、GSTM1、GSTP1和GSTM3）中多态性的分布情况。通过聚合酶链反应（PCR）和PCR-限制性片段长度多态性（RFLP）分析基因型。患者和对照之间GSTM1缺失和GSTM3BB基因型的频率没有差异。与对照相比，GSTT1缺失的总体频率在病例中较低（p = 0.003，优势比（OR）= 0.2，95%置信区间（CI），0.1 - 0.6）。按性别分层后，GSTT1缺失频率仅在女性患者中降低（p = 0.008，OR = 0.2，95% CI = 0.1 - 0.6）。然而，病例中GSTP1的ile/val基因型和val等位基因显著高于对照（分别为p = 0.013，OR = 1.9，95% CI = 1.1 - 3.1；p = 0.027，OR = 1.5，95% CI = 1.0 - 2.1）。为了研究基因-基因相互作用，并结合GSTM1和GSTT1的缺失等位基因或GSTM3的B等位基因，计算了因ile/val或val/val导致的胆囊癌综合风险，但风险没有增加。57.5%的胆囊癌患者有胆结石，但有或没有胆结石的患者之间，所研究的GST基因多态性的等位基因/基因型频率没有显著差异。据我们所知，这是第一篇表明GSTP1的ile/val基因型和val等位基因与胆囊癌高风险相关的论文。
