Department of Health Risk Management, China Medical University, Taichung, Taiwan.
Carcinogenesis. 2010 Feb;31(2):228-33. doi: 10.1093/carcin/bgp286. Epub 2009 Nov 23.
Oxidative stress has been associated with the carcinogenesis of colorectal cancer. Glutathione S-transferases (GSTs) modulate the elimination of free radical. We conducted a case-control study to examine the interaction between oxidative stress and GSTs polymorphisms on colorectal cancer risk. This study recruited 727 pathologically confirmed colorectal adenocarcinoma cases and 736 sex- and age-matched controls. Plasma protein carbonyls, as a parameter of oxidative stress, were measured using enzyme-linked immunosorbent assay. Genotypes of GSTM1, GSTT1 and GSTP1 genes were determined using polymerase chain reaction methods. The protein carbonyl levels were significantly higher in cases than in controls and exerted a dose-response relationship (P for trend < 0.001). Compared with the first carbonyl quartile subjects, those in the second, third and fourth quartiles had odds ratios (ORs) of 1.54 [95% confidence interval (CI) = 1.13-2.10], 1.52 (95% CI = 1.11-2.07) and 1.98 (95% CI = 1.46-2.67), respectively. This effect was significantly modified by GSTM1 genotype (P for interaction = 0.037). The three-way interaction analysis revealed that interactions between GSTM1 genotype and cigarette smoking and between GSTT1 genotype and alcohol drinking further modified the oxidative stress contribution for colorectal cancer (p for interaction were 0.067 and 0.054, respectively). The impact of oxidative stress was more prominent among ever-smokers with GSTM1-null genotype (OR = 3.45, 95% CI = 1.70-6.97) and ever-drinkers with GSTT1-present genotype (OR = 3.87, 95% CI = 1.82-8.25). Our results indicate that interaction between oxidative stress and GSTs polymorphisms may play an important role in the pathogenesis of colorectal cancer.
氧化应激与结直肠癌的发生有关。谷胱甘肽 S-转移酶 (GSTs) 调节自由基的消除。我们进行了一项病例对照研究，以检验氧化应激与 GSTs 多态性在结直肠癌风险中的相互作用。这项研究招募了 727 名经病理证实的结直肠腺癌病例和 736 名性别和年龄匹配的对照。使用酶联免疫吸附试验测量血浆蛋白羰基作为氧化应激的参数。使用聚合酶链反应方法确定 GSTM1、GSTT1 和 GSTP1 基因的基因型。病例组的蛋白羰基水平明显高于对照组，并呈现出剂量反应关系（趋势 P<0.001）。与第一羰基四分位的受试者相比，第二、第三和第四四分位的受试者的比值比 (OR) 分别为 1.54 [95%置信区间 (CI) = 1.13-2.10]、1.52 (95% CI = 1.11-2.07) 和 1.98 (95% CI = 1.46-2.67)。这种影响明显受到 GSTM1 基因型的修饰（交互作用 P 值=0.037）。三向交互分析显示，GSTM1 基因型与吸烟以及 GSTT1 基因型与饮酒之间的相互作用进一步修饰了氧化应激对结直肠癌的贡献（交互作用 P 值分别为 0.067 和 0.054）。在 GSTM1 缺失基因型的既往吸烟者（OR=3.45，95%CI=1.70-6.97）和 GSTT1 存在基因型的既往饮酒者（OR=3.87，95%CI=1.82-8.25）中，氧化应激的影响更为显著。我们的结果表明，氧化应激与 GSTs 多态性之间的相互作用可能在结直肠癌的发病机制中起重要作用。
