Department of Epidemiology and Public Health, National University of Singapore, Singapore.
Carcinogenesis. 2011 Oct;32(10):1507-11. doi: 10.1093/carcin/bgr175. Epub 2011 Jul 29.
Cigarette smoking is a risk factor for colorectal cancer. Putative colorectal procarcinogens in tobacco smoke include polycyclic aromatic hydrocarbons and heterocyclic aromatic amines that are known substrates of glutathione S-transferases (GSTs). This study examined the influence of functional GST gene polymorphisms on the smoking-colorectal cancer association in a population known to be minimally exposed to dietary sources of these procarcinogens. Incident cases of colorectal cancer (n = 480) and matched controls (n = 1167) were selected from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 men and women who have been followed since 1993. We determined the deletion polymorphisms of GSTM1 and GSTT1 and the functional polymorphism at codon 105 of GSTP1 for each subject. A three level composite GST index was used to examine if GST profile affected a smoker's risk of developing colorectal cancer. While there was no statistically significant association between cigarette smoking and colorectal cancer risk among subjects absent of any at-risk GST genotypes, smokers possessing two to three at-risk GST genotypes exhibited a statistically significant increased risk of colorectal cancer compared with non-smokers (P = 0.0002). In this latter stratum, heavy smokers exhibited a >5-fold increased risk relative to never-smokers (odds ratio, 5.43; 95% confidence interval, 2.22-13.23). Subjects with one at-risk GST genotype displayed a statistically significant but weaker association with smoking. These findings suggest that GST gene polymorphisms influence interindividual susceptibility to smoking-associated colorectal cancer. Our data indicate an important role for GST enzymes in the detoxification of colorectal carcinogens in tobacco smoke.
吸烟是结直肠癌的一个危险因素。烟草烟雾中的潜在结直肠前致癌物包括多环芳烃和杂环芳香胺，它们是谷胱甘肽 S-转移酶 (GSTs) 的已知底物。本研究在一个已知很少接触这些前致癌物饮食来源的人群中，研究了功能性 GST 基因多态性对吸烟与结直肠癌关联的影响。结直肠癌病例（n=480）和匹配对照（n=1167）均选自新加坡华人健康研究，这是一项基于人群的前瞻性队列研究，纳入了 63257 名男性和女性，自 1993 年以来一直随访。我们确定了每个研究对象的 GSTM1 和 GSTT1 缺失多态性以及 GSTP1 密码子 105 的功能多态性。使用三个水平的复合 GST 指数来检查 GST 谱是否影响吸烟者患结直肠癌的风险。虽然在没有任何危险 GST 基因型的受试者中，吸烟与结直肠癌风险之间没有统计学上的显著关联，但与非吸烟者相比，携带 2 到 3 个危险 GST 基因型的吸烟者患结直肠癌的风险显著增加（P=0.0002）。在后者中，重度吸烟者的风险相对从不吸烟者增加了 5 倍以上（比值比，5.43；95%置信区间，2.22-13.23）。具有一个危险 GST 基因型的受试者与吸烟之间存在统计学上显著但较弱的关联。这些发现表明 GST 基因多态性影响个体对吸烟相关结直肠癌的易感性。我们的数据表明 GST 酶在烟草烟雾中结直肠致癌物的解毒中起重要作用。
