期刊
MOLECULAR CARCINOGENESIS
卷 49, 期 11, 页码 974-980出版社
WILEY-BLACKWELL
DOI: 10.1002/mc.20682
关键词
genetic epistasis; microsomal epoxide hydrolase; cytochrome P-450 CYP1A1; gene-environment interaction
资金
- NIH Cancer Center [CA16672]
- National Cancer Institute [CA57730, CA070759, CA133996]
The metabolism of xenobiotics is complex and involves multiple steps and multiple enzymes. Genetic variation in the genes encoding these enzymes as well as the level of exposure to the substrates of these enzymes could alter metabolism and clearance of potential carcinogens and thus alter cancer susceptibility. This study examined interaction effect between smoking and two single nucleotide polymorphisms (SNPs)-CYP1A1 c.1384A > G (p.Ile462Val) and EPHX1 c.337T > C (p.Tyr113His)-in modulating colorectal cancer (CRC) risk. The SNPs were selected a priori based on functional significance. In a case-only analysis, unconditional logistic regression was used to examine the associations between smoking and each SNP and between the two SNPs in 786 patients with nonfamilial CRC. There was significant multiplicative interaction for CRC risk between smoking and EPHX1 c.337T > C (odds ratio [OR]=1.37, 95% confidence interval [CI]=1.03-1.81, P=0.03), particularly among smokers with a history of greater than 20 pack-years of smoking (OR=1.52, 95% CI=1.07-2.16, P=0.02). In addition, there was gene-gene interaction between EPHX1 c.337T > C and CYP1A1 c.1384A > G (OR=1.61, 95% CI=1.02-2.55, P=0.04). Smokers with any variant allele of EPHX1 were at increased risk for CRC, as were individuals with any variant allele of CYP1A1 together with any variant allele of EPHX1. Thus, the study of gene-environment and gene-gene interactions may help to identify high-risk subgroups that can be targeted for intensive smoking cessation and CRC screening interventions. (C) 2010 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据