Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer

• Published in: Carcinogenesis (New York) Vol. 29; no. 7; pp. 1386 - 1393
• Main Authors: Yuan, Jian-Min, Chan, Kenneth K., Coetzee, Gerhard A., Castelao, J.Esteban, Watson, Mary A., Bell, Douglas A., Wang, Renwei, Yu, Mimi C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Arylamine N-Acetyltransferase - genetics; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Bladder cancer; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - metabolism; Carcinoma, Transitional Cell - chemically induced; Carcinoma, Transitional Cell - enzymology; Carcinoma, Transitional Cell - genetics; Case-Control Studies; Chemical agents; Cytochrome P-450 CYP1A2 - genetics; Cytochrome P-450 CYP1A2 - metabolism; Female; Genetic Predisposition to Disease; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Medical sciences; Middle Aged; Molecular Epidemiology; Nephrology. Urinary tract diseases; Tumors; Tumors of the urinary system; Urinary Bladder - drug effects; Urinary Bladder - enzymology; Urinary Bladder Neoplasms - chemically induced; Urinary Bladder Neoplasms - enzymology; Urinary Bladder Neoplasms - genetics; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urinary system disease; Toxicity; Risk; Urinary tract disease; Malignant tumor; Metabolism; Bladder cancer; Genetic determinism; Carcinogen; Urinary system; Urinary bladder; Risk factor; Bladder disease; Cancer
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/bgn136

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual’s susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case–control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19–48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19–1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12–1.81) and 1.71 (1.25–2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12–3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype.