Molecular epidemiology and urothelial cancer.
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 GSTM1 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.
Tsukino
Hiromasa
H
Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Omori
Hisamitsu
H
Kohshi
Kiyotaka
K
Yamano
Yuko
Y
Katoh
Takahiko
T
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D015238:Sulfotransferases / Q000235:genetics; D014571:Urologic Neoplasms / Q000453:epidemiology* / Q000209:etiology; D019459:Urothelium
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; D005982:Glutathione Transferase; D015238:Sulfotransferases