Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas
Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas
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DOI：
10.1002/ijc.11533
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发表时间：
2004-01-01
影响因子：
6.4
通讯作者：
Kampman, E
中科院分区：
文献类型：
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作者：
Tiemersma, EW;Bunschoten, A;Kampman, E
香烟烟雾中含有多环碳氢化合物和芳香胺，它们都可以被SULT 1A 1编码的磺基转移酶激活。遗传多态性导致Arg 213 His取代，从而降低酶的活性和稳定性，并可能因此改变吸烟和结直肠腺瘤之间的关联。我们在一项荷兰病例对照研究中对此进行了调查。此外，我们评估了环氧化物水解酶（EPHX），N-乙酰转移酶（NAT 1和NAT 2）和谷胱甘肽S-转移酶（GSTM 1和GSTT 1）的潜在作用。数据分析包括431例腺瘤病例和432例无息肉对照（54%为女性，平均年龄54.6岁），这些病例在1997年至2000年期间在8家荷兰医院接受内窥镜检查。所有参与者都提供了吸烟习惯和血液DNA分离的数据。采用适当的聚合酶链反应-限制性片段长度多态性方法进行基因分型。多变量模型包括年龄、性别、内窥镜检查适应症、零食和酒精摄入量，以及每日吸烟剂量或吸烟持续时间（如适用）。吸烟增加结直肠腺瘤的风险，最重要的是持续时间。与从不吸烟相比，吸烟超过25年的腺瘤风险增加一倍以上（OR = 2.4，95%CI = 1.4-4.1）。SULTIAI快速硫酸化（*1/*1）和NAT 2缓慢乙酰化与吸烟的组合导致腺瘤风险比具有其他遗传基因变体的从不吸烟者高4倍，尽管没有统计学显著性效应修饰。我们没有发现其他基因多态性对吸烟和腺瘤之间的关联有明显的影响。我们的结论是，吸烟增加结直肠腺瘤的风险，SULT 1A 1和NAT 2只是适度修改这种关联。(C)2003 Wiley-Liss，Inc.
Cigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case-control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N-acetyltransferases (NAT1 and NAT2) and glutathione S-transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp-free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction-restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% Cl = 1.4-4.1) compared to never smoking. Combinations of SULTIAI fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association. (C) 2003 Wiley-Liss, Inc.