Investigation of interaction between N-acetyltransferase 2 and heterocyclic amines as potential risk factors for colorectal cancer
Investigation of interaction between N-acetyltransferase 2 and heterocyclic amines as potential risk factors for colorectal cancer
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DOI：
10.1093/carcin/24.2.275
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发表时间：
2003-02-01
期刊：
影响因子：
4.7
通讯作者：
Forman, D
中科院分区：
文献类型：
--
作者：
Barrett, JH;Smith, G;Forman, D
快速 N-乙酰转移酶 2 (NAT2) 乙酰化剂可能会通过激活致癌杂环胺 (HA) 增加患结直肠癌的风险，这些胺是由高温烹调的肉类产生的，存在于香烟烟雾中。英国对 500 例结直肠癌病例和人群对照进行了一项研究，对年龄、性别和全科医生进行了匹配，以调查这一假设。通过访谈进行的详细调查问卷评估了通常的肉类摄入量和终生吸烟习惯。受试者还表明他们吃的肉做得有多好。根据 NAT2 基因型，将受试者分为快速或慢速 NAT2 乙酰化者。 433 对匹配的完整基因型数据可用。结直肠癌的风险随着肉类摄入量的增加而稳步增加，在调整总能量摄入量后，最高四分位数与最低四分位数的比值比上升至 1.51 [95% 置信区间 (1.03, 2.23)]，红肉的比值比更明显 [比值比 1.97 (1.30, 2.98)]。然而，这种效果并没有受到对全熟肉的偏好的影响。吸烟还与风险增加相关[曾经吸烟者与从不吸烟者的比值比为 1.47 (1.10, 1.98)]。在这两种情况和对照中，大约 40% 的受试者被归类为快速乙酰化者，并且与（红）肉摄入和吸烟相关的风险不随 NAT2 状态而变化。这项研究并没有支持这样的假设：即使暴露于煮熟的肉类或吸烟中产生的高水平 HA，快速 NAT2 乙酰化剂也会增加患结直肠癌的风险。
Fast N-acetyltransferase 2 (NAT2) acetylators may be at increased risk of colorectal cancer through the activation of carcinogenic heterocyclic amines (HA), which are produced by meat cooked at high temperatures and are found in cigarette smoke. A study of 500 incident colorectal cancer cases and population controls, matched for age, sex and general practitioner, was conducted in the UK to investigate this hypothesis. Usual meat intake and lifetime smoking habits were estimated using a detailed questionnaire administered by interview. Subjects also indicated how well cooked they ate their meat. Subjects were classified as fast or slow NAT2 acetylators on the basis of NAT2 genotype. Complete genotype data were available on 433 matched pairs. The risk of colorectal cancer showed a steady increase with meat intake, rising to an odds ratio of 1.51 [95% confidence interval (1.03, 2.23)] for the highest versus the lowest quartile, after adjustment for total energy intake, and this was even more pronounced for red meat [odds ratio 1.97 (1.30, 2.98)]. However, this effect was not influenced by the preference for well-done meat. Smoking was also associated with an increased risk [odds ratio 1.47 (1.10, 1.98) for ever- versus never-smokers]. In both cases and controls similar to40% of subjects were classified as fast acetylators, and the risks associated with (red) meat intake and smoking did not vary with NAT2 status. This study provides no support for the hypothesis that fast NAT2 acetylators are at increased risk of colorectal cancer, even if exposed to high levels of HA from well-cooked meat or smoking.