Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control study.
OBJECTIVE
This study was conducted to examine whether certain slow N-acetylation genotypes could be risk factors for bladder cancer, and the possible association between specific genotypes and the severity of the disease at first diagnosis.


METHODS
This case-control study included 89 patients with transitional cell bladder cancer (diagnosed over a period of 21 months) and 147 controls. N-acetyltransferase-2 (NAT-2) genotypes were identified by allele specific polymerase chain reaction (PCR) on peripheral blood DNA samples. The x2 test was used for statistical evaluation to compare the differences observed between patients and controls and the different genotypes with tumor grading and local staging at presentation. Relative, attributable and population attributable risks were estimated for the genotypes found to present a significantly increased frequency for bladder cancer.


RESULTS
A statistically significant difference in the frequency of genotypes was found between the two groups. The patient group had the higher frequency of slow acetylation genotypes (p = 0.0016). Among slow acetylators, homozygotes 341C/341C and compound heterozygotes 341C/857A had the most excessive risk for bladder cancer (p = 0.0041 and 0.0031, respectively). The 341C/341C genotype was found to be associated with more aggressive disease, in terms of tumor grading at presentation (p <0.05).


CONCLUSIONS
According to our data, slow acetylators with 341C/341C and 341C/857A genotypes carry a substantially higher odds ratio (3.73 and 12.46, respectively) for bladder carcinogenesis. Additionally, among the slow acetylators, 341C/341C homozygotes are likely to have a higher risk for more aggressive disease.
Filiadis
I F
IF
Department of Urology, Medical School of Ioannina University and Ioannina University Hospital, Greece.
Georgiou
I
I
Alamanos
Y
Y
Kranas
V
V
Giannakopoulos
X
X
Lolis
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics*
D001191:Arylamine N-Acetyltransferase