Association of NAT2, GSTM1, GSTT1, CYP2A6, and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China.
OBJECTIVE
To explore the association of polymorphisms in N-acetyltransferase 2 (NAT2), glutathione S-transferase (GST), cytochrome P450 (CYP) 2A6, and CYP 2A13 genes with susceptibility and clinicopathologic characteristics of bladder cancer in a Chinese population.


METHODS
In a hospital-based case-control study of 208 cases and 212 controls matched on age and gender, genotypes were determined by PCR-based methods. Risks were evaluated by unconditional logistic regression analysis.


RESULTS
It was found that significant associations of the NAT2 slow-acetylator genotype (odds ratio, OR: 2.42; 95% confidence interval, CI: 1.47-3.99), GSTM1 null genotype (OR: 1.64; 95% CI: 1.11-2.42) and GSTM1/GSTT1-double null genotype (OR: 1.72; 95% CI: 1.00-2.95) with increased risk of bladder cancer. Conversely, carriers with at least one CYP2A6*4 allele showed lower risk than the non-carriers (OR: 0.47; 95% CI: 0.28-0.79). The adjusted ORs (95% CI) for smokers with NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null genotype, and variant CYP2A6 genotypes were 2.99 (1.44-6.25), 1.98 (1.13-3.48), 2.66 (1.22-5.81) and 0.41 (0.20-0.86), respectively. Furthermore, NAT2 slow-acetylator, GSTM1 null, and GSTM1/GSTT1-double null genotypes were associated with higher tumor grade (P=0.001, 0.022, and 0.036, respectively), and only NAT2 slow-acetylator genotype was associated with higher tumor stage (P=0.007). CYP2A13 was not associated with risk or tumor characteristics.


CONCLUSIONS
It is suggested that NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null, and variant CYP2A6 genotypes may play important roles in the development of bladder cancer in Henan area, China.
Song
Dong-Kui
DK
Department of Urology, First Affiliated Hospital, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China.
Xing
Dong-Liang
DL
Zhang
Li-Rong
LR
Li
Zhong-Xue
ZX
Liu
Jian
J
Qiao
Bao-Ping
BP
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D065637:Cytochrome P-450 CYP2A6; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
D001189:Aryl Hydrocarbon Hydroxylases; D001191:Arylamine N-Acetyltransferase; D065637:Cytochrome P-450 CYP2A6; D005982:Glutathione Transferase; C414206:CYP2A13 protein, human; C585710:CYP2A6 protein, human; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1