N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men.
BACKGROUND
The purpose of this study was to determine the frequency of a polymorphism of the candidate metabolic enzyme N-acetyltransferase-2 (NAT2) in Japanese prostate cancer patients and Japanese non-cancer controls, in order to determine if an association exists between NAT2 genotype and the occurrence, clinical stage and grade of prostate cancer.


METHODS
In the present case-control study, 111 patients with prostate cancer and 152 controls were genotyped for the NAT2 polymorphism using the polymerase chain reaction-based restriction fragment length polymorphism method. The NAT2 genotypes (slow or rapid acetylator genotype) were determined by the combination of three known NAT2 mutant alleles (M1, M2, M3) and the wild-type allele.


RESULTS
The NAT2 slow acetylator genotype was statistically higher among prostate cancer patients (17.1%) compared with controls (8.6%) (Odds ration (OR) = 2.21; 95% confidence interval (CI), 1.04-4.69; P = 0.0289). In addition, there was a statistically increased risk of prostate cancer among smokers with the NAT2 slow genotype (OR = 3.78: 95% CI, 1.48-9.66; P = 0.0041). Furthermore, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with locally advanced and metastatic disease (22.7%) compared with controls (8.6%) (OR = 3.14; 95% CI, 1.40-7.06; P = 0.0051). Lastly, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with high-grade tumors (31.4%) compared with controls (8.6%) (OR = 4.90; 95% CI, 1.97-12.20; P = 0.0010).


CONCLUSIONS
These data demonstrate that the NAT2 slow acetylator genotype plays an important role in determining the risk of developing prostate cancer in Japanese men and is also associated with more clinically advanced and pathologically aggressive disease. Furthermore, a possible interaction between the NAT2 slow acetylator genotype and smoking status was suggested.
Hamasaki
Takashi
T
Department of Urology, University of Occupational and Environmental Health, Fukuoka, Japan. t-hama@fukushima-rosai.jp
Inatomi
Hisato
H
Katoh
Takahiko
T
Aono
Hisami
H
Ikuyama
Toshihiro
T
Muratani
Tetsuro
T
Matsumoto
Tetsuro
T
D000107:Acetylation; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human