Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps
Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps
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DOI：
10.1093/carcin/bgl135
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发表时间：
2007-02-01
期刊：
影响因子：
4.7
通讯作者：
Bigler, Jeannette
中科院分区：
文献类型：
--
作者：
Goode, Ellen L.;Potter, John D.;Bigler, Jeannette
暴露在香烟烟雾和肉类等环境中含有多种致癌原，它们被认为在增加结直肠息肉和/或癌症的风险方面发挥了作用。这些前致癌物(包括杂环胺和多环芳烃)被多种多态酶代谢，包括N-乙酰基转移酶、磺基转移酶、细胞色素P450酶和环氧化物水解酶。我们假设编码基因NAT1、NAT2、SULT1A1、SULT1A2、CYP1A1或EPHX1的遗传变异与大肠息肉的风险相关，并与吸烟或肉类摄入量相互作用来改变大肠息肉的风险。我们在一项基于临床的研究中检验了这些基因在651例患有增生性息肉、腺瘤性息肉或这两种类型的息肉的高加索人和556例无息肉的对照组中的作用。我们发现NAT乙酰化状态和SULT1A1基因在增生性息肉风险中的交互作用：与SULT1A1 638GG基因和NAT1和NAT2慢速表型相比，携带SULT1A1 638AA和Nat1和Nat2中/快表型的个体患增生性息肉的风险增加3.5倍(95%CI 1.2-10.3)。数据还与吸烟与SULT1A1、CYP1A1和EPHX1变异之间的交互作用以及肉类摄入量与CYP1A1和EPHX1变异之间的交互作用相一致。无交互作用有统计学意义。尽管考虑到样本大小和被检查的假说的数量，我们的研究应该谨慎地解释结果，但我们的研究建议未来在更大范围内对结直肠癌发生途径中的遗传和生活方式因素进行调查。
Exposures such as cigarette smoke and meat contain a variety of procarcinogens, which are thought to play a role in elevation of risk for colorectal polyps and/or cancer. These procarcinogens (including heterocyclic amines and polycyclic aromatic hydrocarbons) are metabolized by a variety of polymorphic enzymes including N-acetyltransferases, sulfotransferases, cytochrome P450 enzymes and epoxide hydrolase. We hypothesized that genetic variation in the encoding genes NAT1, NAT2, SULT1A1, SULT1A2, CYP1A1 or EPHX1 is associated with risk of colorectal polyps and interacts with cigarette use or meat intake to modify risk of colorectal polyps. We examined the role of these genes in a clinic-based study of 651 Caucasian cases with hyperplastic polyps, adenomatous polyps or both types of polyps and 556 polyp-free controls. We found evidence for interaction between NAT acetylator status and SULT1A1 genotype in risk of hyperplastic polyps: individuals with SULT1A1 638AA genotype and NAT1 and NAT2 intermediate/fast phenotypes had 3.5-fold increased risk (95% CI 1.2-10.3) compared with individuals with SULT1A1 638GG genotype and NAT1 and NAT2 slow phenotypes. Data were also consistent with interactions between smoking and variation in SULT1A1, CYP1A1 and EPHX1 and between meat intake and variation in CYP1A1 and EPHX1. No interactions were statistically significant. Although results should be interpreted with caution considering sample size and the number of hypotheses examined, our study suggests future avenues of investigation in larger investigations of genetic and lifestyle factors in the pathway to colorectal cancer.