Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.
Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.
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DOI：
10.1136/gutjnl-2011-300665
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发表时间：
2013-03
期刊：
影响因子：
24.5
通讯作者：
Le Marchand L
中科院分区：
文献类型：
--
作者：
Voutsinas J;Wilkens LR;Franke A;Vogt TM;Yokochi LA;Decker R;Le Marchand L
杂环胺（HAA）是动物致癌物，存在于高温烹饪的肉类和烟草烟雾中。这些化合物需要细胞色素P450 1A 2（CYP 1A 2）和N-乙酰转移酶-2（NAT 2）的活化才能损伤DNA。这项研究测试了这样的假设，即全熟的肉和吸烟会增加腺瘤的风险，腺瘤是大多数结直肠癌的前体，特别是在具有快速CYP 1A 2和快速NAT 2活性的个体中。在高加索人、日本人和夏威夷土著人中进行了一项基于内窥镜的腺瘤病例对照研究，以验证这一假设。通过对1016例首次腺瘤患者和1355例正常内镜检查的对照组进行访谈，评估了总体饮食和各种高温方法烹制的全熟肉的消费量。采用咖啡因试验检测635例患者和845例对照者的CYP 1A 2和NAT 2活性。Logistic回归用于解释匹配因素和潜在混杂因素。吸烟与腺瘤风险增加有关。对于HAA摄入量或NAT 2活性的主要影响，观察到弱的非显著性升高OR。然而，HAA摄入量和NAT 2活性的联合作用具有统计学显著性。与处于NAT 2活性和暴露水平的较低三分位数的受试者相比，处于NAT 2活性和HAA摄入水平的较高三分位数的受试者发生腺瘤的风险增加（2-氨基-3，4，8-二甲基咪唑并[4，5-f]喹喔啉摄入OR 1.70，95%CI 1.06至2.75; 2-氨基-3，8-二甲基咪唑并[4，5-f]喹喔啉摄入OR 1.91，95% CI 1.16至3.16; 2-氨基-1-甲基-6-苯基咪唑并[4，5-B]吡啶摄入OR 2.14，95% CI 1.31至3.49）。这些数据表明，高HAA摄入量的快速N-乙酰化可能会增加腺瘤的风险。
Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities. An endoscopy-based case–control study of adenoma was conducted among Caucasians, Japanese and native Hawaiians to test this hypothesis. The overall diet and consumption of well-done meat cooked by various high-temperature methods were assessed by interview in 1016 patients with a first adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic regression was used to account for matching factors and potential confounders. Smoking was associated with an increased risk of adenoma. Weak non-significant elevated OR were observed for the main effects of HAA intakes or NAT2 activity. However, the combined effects of HAA intakes and NAT2 activity were statistically significant. Subjects in both the upper tertiles of NAT2 activity and HAA intake were at increased risk of adenoma compared with subjects in the lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5-f] quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine intake OR 2.14, 95% CI 1.31 to 3.49). The data suggest that rapid N-acetylators with high HAA intake may be at increased risk of adenoma.
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影响因子：
4.7
作者：
Goode, Ellen L.;Potter, John D.;Bigler, Jeannette
通讯作者：
Bigler, Jeannette
影响因子：
9.8
作者：
Ferrucci, Leah M.;Sinha, Rashmi;Graubard, Barry I.;Mayne, Susan T.;Ma, Xiaomei;Schatzkin, Arthur;Schoenfeld, Philip S.;Cash, Brooks D.;Flood, Andrew;Cross, Amanda J.
通讯作者：
Cross, Amanda J.
影响因子：
5.9
作者：
Cascorbi, I;Brockmöller, J;Roots, I
通讯作者：
Roots, I
影响因子：
3.8
作者：
Lilla, C;Verla-Tebit, E;Chang-Claude, J
通讯作者：
Chang-Claude, J
DOI：
10.1097/00008571-200203000-00008
发表时间：
2002-03-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Ishibe, N;Sinha, R;Rothman, N
通讯作者：
Rothman, N