Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.
Cancer Causes Control. 2009 Dec;20(10):2031-8. doi: 10.1007/s10552-009-9399-7. Epub 2009 Jul 18.
Glutathione S-transferase (GST) enzymes are known to metabolize tobacco-related carcinogens. Previous studies on the association of functional polymorphisms of GST genes with esophageal squamous cell carcinoma have yielded conflicting but overall null results. A few studies of esophageal adenocarcinoma were likewise conflicting, but the scarcity of data is striking. We aimed to study associations of the GSTM1 and GSTT1 null deletion polymorphisms as well as the GSTP1 Ile105Val polymorphism with risks for esophageal and gastric cardia cancers. DNA was prepared from 96 and 79 cases of esophageal adenocarcinoma and squamous cell carcinoma, respectively, 126 cardia cancer cases, and 471 population-based controls. Pyrosequencing typed the GSTP1 Ile105Val polymorphism, while multiplex PCR detected GSTM1 and GSTT1 deletions. Logistic regression modeling estimated odds ratios (ORs) with 95% confidence intervals (CIs). None of the studied polymorphisms were related to the risk of esophageal adenocarcinoma, but the variant GSTP1 Val(105) allele was associated with an increased risk of esophageal squamous cell carcinoma (OR = 1.7; 95% CI 1.0-2.9) and tended to be weakly, positively linked to cardia cancer (OR = 1.4; 95% CI 0.9-2.1). Finally, we performed a meta-analysis and found that GSTP1 polymorphism seems to be associated with the risk of esophageal squamous cell carcinoma among Caucasian population (OR = 1.4; 95% CI 1.0-2.2; p value for heterogeneity test 0.34).
谷胱甘肽 S-转移酶（GST）酶已知可代谢与烟草相关的致癌物质。先前关于 GST 基因功能多态性与食管鳞状细胞癌之间关联的研究得出了相互矛盾但总体上为阴性的结果。少数关于食管腺癌的研究结果也存在矛盾，但数据的缺乏令人震惊。我们旨在研究 GSTM1 和 GSTT1 缺失多态性以及 GSTP1 Ile105Val 多态性与食管和胃贲门癌风险的关联。从 96 例食管腺癌和 79 例食管鳞状细胞癌、126 例贲门癌病例和 471 名基于人群的对照中提取 DNA。焦磷酸测序对 GSTP1 Ile105Val 多态性进行分型，而多重 PCR 则检测 GSTM1 和 GSTT1 缺失。逻辑回归模型估计了比值比（OR）及其 95%置信区间（CI）。在所研究的多态性中，没有一个与食管腺癌的风险相关，但 GSTP1 变体 Val(105)等位基因与食管鳞状细胞癌的风险增加相关（OR = 1.7；95%CI 1.0-2.9），并且与贲门癌呈弱正相关（OR = 1.4；95%CI 0.9-2.1）。最后，我们进行了荟萃分析，发现 GSTP1 多态性似乎与白种人群的食管鳞状细胞癌风险相关（OR = 1.4；95%CI 1.0-2.2；异质性检验 p 值为 0.34）。
