Effect of NAT1 and NAT2 genetic polymorphisms on colorectal cancer risk associated with exposure to tobacco smoke and meat consumption
Effect of NAT1 and NAT2 genetic polymorphisms on colorectal cancer risk associated with exposure to tobacco smoke and meat consumption
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DOI：
10.1158/1055-9965.epi-05-0618
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发表时间：
2006-01-01
影响因子：
3.8
通讯作者：
Chang-Claude, J
中科院分区：
文献类型：
--
作者：
Lilla, C;Verla-Tebit, E;Chang-Claude, J
N-乙酰基转移酶1和2（NAT 1和NAT 2），都是高度多态性的，参与香烟烟雾和高温烹饪技术烹饪的红肉中存在的芳香族和杂环芳香族胺的代谢。我们研究了乙酰化能力的差异，由NAT 1和NAT 2基因型决定，对与暴露于烟草烟雾或红肉消费相关的结直肠癌风险的影响。在这项在德国进行的基于人群的病例对照研究中，纳入了505例偶发结直肠癌患者和604例年龄和性别匹配的对照个体，这些个体具有基因分型数据和详细的风险因素信息。使用基于荧光的熔解曲线分析方法对NAT 1和NAT 2基因多态性进行基因分型。基因型、环境暴露和结直肠癌风险之间的关联使用多变量逻辑回归进行估计。与主动吸烟相关的结直肠癌风险在累积30（+）包年吸烟后升高[比值比（OR），1.4; 95%可信区间（95%CI），0.9-2.2]，但NAT 1或NAT 2基因型均未显著改变。暴露于环境烟草烟雾仅与NAT 2快速乙酰化者的结直肠癌风险增加相关（儿童和成人暴露的OR为2.6; 95%CI为1.1-5.9）。经常食用红肉显著增加了所有NAT 2快速乙酰化者或NAT 1 *10等位基因携带者的结直肠癌风险（OR，2.6; 95%CI，1.1-6.1），但不包括那些“慢”NAT 1和NAT 2基因型。我们的研究结果表明，NAT 1和NAT 2基因型可能共同有助于个体的易感性，杂环芳香胺可能在与红肉相关的结直肠癌中发挥重要作用，也可能暴露于环境烟草烟雾。
N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are involved in the metabolism of aromatic and heterocyclic aromatic amines present in cigarette smoke and red meat cooked by high-temperature cooking techniques. We investigated the effect of differences in acetylation capacity, determined by NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to tobacco smoke or red meat consumption. In this population-based case-control study in Germany, 505 patients with incident colorectal cancer and 604 age- and sex-matched control individuals with genotyping data and detailed risk factor information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was done using a fluorescence-based melting curve analysis method. The association between genotypes, environmental exposures, and colorectal cancer risk was estimated using multivariate logistic regression. Colorectal cancer risk associated with active smoking was elevated after accumulation of 30(+) pack-years of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9-2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to environmental tobacco smoke was associated with an increased risk for colorectal cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in childhood and adulthood). Frequent consumption of red meat significantly increased colorectal cancer risk for the group comprising all NAT2 fast acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% Cl, 1.1-6.1) but not among those with "slow" NAT1 and NAT2 genotypes. Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke.