International Centre for Genetic Engineering and Biotechnology (ICGEB), UCT Campus, Anzio Road Observatory 7925, Cape Town, South Africa.
BMC Genet. 2010 Jun 11;11:47. doi: 10.1186/1471-2156-11-47.
The Glutathione S-transferases (GSTs) comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study the effects of polymorphisms in these genes on the risk of developing oesophageal squamous cell carcinoma (OSCC) were evaluated in a hospital-based case-control study in two South African population groups. Genetic polymorphisms in GSTs were investigated in 245 patients and 288 controls samples by PCR-RFLP analysis.
The GSTP1 341T variant was associated with significantly increased risk of developing OSCC as observed from the odds ratios for the GSTP1 341C/T and GSTP1 341T/T genotypes (OR = 4.98; 95%CI 3.05-8.11 and OR = 10.9; 95%CI 2.43-49.1, respectively) when compared to the homozygous GSTP1 341C/C genotype. The risk for OSCC in the combined GSTP1 341C/T and T/T genotypes was higher in tobacco smokers (OR = 7.51, 95% CI 3.82-14.7), alcohol consumers (OR = 15.3, 95% CI 1.81-12.9) and those using wood or charcoal for cooking and heating (OR = 12.1, 95% CI 3.26-49) when compared to those who did not smoke tobacco, or did not consume alcohol or user other forms of fuel for cooking and heating. Despite the close proximity of the two GSTP1 SNPs (313A>G and 341C>T), they were not in linkage disequilibrium in these two population groups (D':1.0, LOD: 0.52, r2: 0.225). The GSTP1 313A/G polymorphism on the other hand, did not display any association with OSSC. The homozygous GSTT10 genotype was associated with increased risk of OSCC (OR = 1.71, 95%CI 1.18-2.46) while the homozygous GSTM10 genotype was associated with significantly decreased risk of OSCC in the Mixed Ancestry subjects (OR= 0.39, 95%CI 0.25-0.62).
This study shows that the risk of developing OSCC in the South African population can be partly explained by genetic polymorphisms in GST coding genes and their interaction with environmental factors such as tobacco smoke and alcohol consumption.
谷胱甘肽 S-转移酶（GSTs）是一组在致癌物解毒中起关键作用的酶。在这项研究中，通过在南非两个人群的基于医院的病例对照研究，评估了这些基因的多态性对发展食管鳞状细胞癌（OSCC）的风险的影响。通过 PCR-RFLP 分析，在 245 例患者和 288 例对照样本中研究了 GSTs 的遗传多态性。
与 GSTP1 341C/C 纯合基因型相比，GSTP1 341C/T 和 GSTP1 341T/T 基因型的 GSTP1 341T 变体观察到的优势比（OR = 4.98；95%CI 3.05-8.11 和 OR = 10.9；95%CI 2.43-49.1）与 OSCC 发病风险显著相关。在同时吸烟、饮酒以及使用木材或木炭烹饪和取暖的人群中（与不吸烟、不饮酒或不使用其他形式燃料烹饪和取暖的人群相比），GSTP1 341C/T 和 T/T 基因型的 OSCC 风险更高（OR = 7.51，95%CI 3.82-14.7；OR = 15.3，95%CI 1.81-12.9；OR = 12.1，95%CI 3.26-49）。尽管 GSTP1 中的两个 SNP（313A>G 和 341C>T）非常接近，但在这两个人群中它们没有处于连锁不平衡状态（D'：1.0，LOD：0.52，r2：0.225）。另一方面，GSTP1 313A/G 多态性与 OSSC 无关。在混合血统人群中，纯合 GSTT10 基因型与 OSCC 风险增加相关（OR = 1.71，95%CI 1.18-2.46），而纯合 GSTM10 基因型与 OSCC 风险显著降低相关（OR = 0.39，95%CI 0.25-0.62）。
本研究表明，南非人群中 OSCC 的发病风险可以部分归因于 GST 编码基因的遗传多态性及其与环境因素（如吸烟和饮酒）的相互作用。
