原创力文档effect of genetic polymorphism of cyp2a6 on individual susceptibility to colorectal tumors in japanese smokers体内cyp2a6基因表现的遗传多态性对个人的影响在日本吸烟者对结直肠肿瘤的易感性.pdfVIP
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effect of genetic polymorphism of cyp2a6 on individual susceptibility to colorectal tumors in japanese smokers体内cyp2a6基因表现的遗传多态性对个人的影响在日本吸烟者对结直肠肿瘤的易感性
Journal of Cancer Therapy, 2012, 3, 207-215 207
/10.4236/jct.2012.34030 Published Online August 2012 (http://www.SciRP.org/journal/jct)
Effect of Genetic Polymorphism of CYP2A6 on Individual
*
Susceptibility to Colorectal Tumors in Japanese Smokers
1 1 1 2 3
Asami Muroi , Kazuma Kiyotani , Masaki Fujieda , Hideki Ishikawa , Tatsuya Takeshita ,
Shunsuke Iwano1, Hiroshi Yamazaki1,4#, Tetsuya Kamataki1
1Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; 2Department
of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University, Kyoto, Japan; 3Department of Public Health, Wakayama
Medical University, Wakayama, Japan; 4Showa Pharmaceutical University, Tokyo, Japan.
Email: #hyamazak@ac.shoyaku.ac.jp
Received May 10th, 2012; revised June 12th, 2012; accepted June 29th, 2012
ABSTRACT
Tobacco smoking is a risk factor for colorectal cancer and adenomas. To clarify the effect of genetic factors on the risk
for tobacco-related colorectal tumors in a Japanese population, we performed a case-control study on 300 patients with
two or more tumors and 181 healthy controls; all were genotyped for CYP2A6*4, CYP2A6*7 and CYP2A6*9. Cigarette
smoking increased colorectal tumor risk (trend-test P 0.0000005). Current smokers plus ex-smokers (ever-smokers)
with the CYP2A6*4/*4 genotype (whole gene deletion) showed the lowest risk among smokers [odds ratio (OR), 0.17;
95% confidence interval (CI), 0.05 - 0.62 compared to ever-smokers with the wild-type CYP2A6*1/*1]. When the par-
ticipants were classified into four phenotype groups based on estimated CYP2A6 activi
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