Open AccessUrothelial Cancer Risk in Relation to Genotypes of Glutathione S‐Transferase ( GST ) M1, T1, P1 and N‐Acetyltransferase 2 ( NAT2 ), and Tobacco Smoking
Author(s) -
Katoh Takahiko,
Nakano Masahiro,
Yoshioka Makoto,
Inatomi Hisato,
Matsumoto Tetsuro,
Kawamoto Toshihiro
Publication year - 1999
Publication title -
journal of occupational health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 59
ISSN - 1348-9585
DOI - 10.1539/joh.41.12
Subject(s) - genotype , odds ratio , gstp1 , bladder cancer , glutathione s transferase , confidence interval , oncology , medicine , cancer , biology , genetics , physiology , gynecology , glutathione , gene , enzyme , biochemistry
Urothelial Cancer Risk in Relation to Genotypes of Glutathione S‐Transferase ( GST ) M1, T1, P1 and N‐Acetyltransferase 2 (NAT2) , and Tobacco Smoking: Takahiko K atoh , et al . Department of Health Information Science, School of Health Sciences —Both genetic and environmental factors are involved in the development of cancer. Molecular epidemiological studies were performed in order to elucidate the relationship between four polymorphic metabolic enzymes and susceptibility to urothelial cancer (bladder, renal pelvis and ureter) and cigarette‐smoking. The polymorphisms of glutathione S‐transferase ( GST ) M1, T1 and P1 , and N‐acetyltransferase (NAT) 2 were analyzed by PCR, and a history of cigarette smoking was obtained through an interview with 102 cancer cases and with 100 controls. GSTM1 null genotype was a risk factor (odds ratio (OR), 2.12; 95% confidence interval (Cl), 1.17‐3.90), especially in smokers (OR, 3.70; 95%CI, 1.16‐12.79). GSTT1 null genotype and the polymorphism of GSTP1 at nucleotide 313 were not associated with the cancer risk. Slow acetylation genotype of NAT2 was a significant risk factor (OR, 4.75; 95%CI, 1.64‐15.90) in overall samples and the greatest risk for smokers (OR, 10.05; 95% Cl, 1.08‐240.6). To investigate the relationship between the cancer and the amount of smoking, we performed regression analysis for the relative risk of cancer as a function of the amount of smoking. The regression analysis shows that the susceptibility of people who have the GSTM1 null genotype or NAT2 intermediate acetylator genotype is easily raised by a little smoking compared to the GSTM1 positive genotype or NAT2 rapid acetylation genotype, respectively. These results imply that polymorphisms in the GSTM1 and NAT2 gene are a genetic determinant of urothelial cancer among Japanese, and the interaction between genes and cigarette smoking may be important in the development of urothelial cancer.