@article{oai:kumadai.repo.nii.ac.jp:00024284,
 author = {Tsukino, Hiromasa and Omori, Hisamitsu and Kohshi, Kiyotaka and Yamano, Yuko and Katoh, Takahiko and 月野, 浩昌 and 大森, 久光 and 合志, 清隆 and 山野, 優子 and 加藤, 貴彦},
 issue = {3},
 journal = {産業医科大学雑誌},
 month = {Sep},
 note = {application/pdf, 論文(Article), 喫煙は尿路上皮がんの主要な原因の一つであるが,すべての喫煙者ががんに罹患するわけではない.この事象から,尿路上皮がんのリスク要因として,遺伝的背景の存在が示唆されてきた.タバコの煙には多くのがん原性化学物質が含まれており,これらは第I相,第II相の薬物代謝酵素によって活性化,解毒される.従ってDNAと反応する究極がん原性物質の量は,活性化と解毒の代謝的バランスによって決定されると考えられる.近年,薬物代謝酵素には遺伝子多型の存在が明らかとなり,シトクロームP450,グルタチオンS-トランスフェラーゼ(GST),N-アセチルトランスフェラーゼ(NAT),スルフォトランスフェラーゼの遺伝子多型と尿路上皮がんとの関連性に関する多数の分子疫学研究が実施されている.GSTMl遺伝子欠損型,NAT2遅延型では軽度のリスクの上昇が報告されているが,他の薬物代謝酵素との関連性については一致した結果が得られていない.これらの関連性を明らかにするためには,優れた研究デザインによる大規模研究が必要である., Tobacco smoking is the main cause of human urothelial cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops urothelial cancer. Tobacco smoke contains many carcinogens which are activated or detoxified by phase-I or phase-II enzymes. The concentration of the ultimate carcinogen, which will react with DNA, is determined by the rate of activation and detoxification. Individuals with an increased rate of activation or a decreased rate of detoxification have a slightly higher level of bulky carcinogen-DNA adduct in the urothelial mucosa. Thus metabolic polymorphisms have been recognized as important determinants of carcinogen susceptibility, and recent efforts have shown that inter-individual differences in specific cytochrome P450 enzymes (CYPs), N-acetyltransferases (NAT), glutathione S-transferases (GST) and sulfotransferases (SULT) are often disproportionately represented in epidemiological studies between urothelial cancer cases and controls. It has been revealed that GSTMl null genotype or NAT2 slow acetylator genotype may be associated with a small increase in urothelial cancer risk. Associations between other polymorphisms of metabolic enzymes and urothelial cancer are not well-known or are inconsistent. To reveal these associations, further well-designed and large-scale studies are needed., http://ci.nii.ac.jp/naid/110006381795},
 pages = {265--289},
 title = {分子疫学と尿路上皮がん},
 volume = {29},
 year = {2007}
}