MnSOD genotype and prostate cancer risk as a function of NAT genotype and smoking status.
BACKGROUND
Cigarette smoke contains carcinogenic aromatic and heterocyclic amines that are metabolized by N-acetyltransferase (NAT). These carcinogens also produce reactive oxygen species that are metabolized by manganese superoxide dismutase (MnSOD). The association between prostate cancer (PCA) and the polymorphism of MnSOD and NAT, and cigarette smoking was investigated.


METHODS
DNA samples from 187 PCA patients and 175 age-matched controls were genotyped for MnSOD, NAT1 and NAT2 by PCR restriction fragment length polymorphism analysis and DNA sequencing.


RESULTS
MnSOD AA genotype, as compared to MnSOD VV and VA, was associated with PCA (odds ratio, 1.65; 95% confidence interval, 1.03-2.66. There was no association of PCA with NAT or smoking. Results of exploratory analyses of the data suggest that the association of PCA and MnSOD exists only in the subpopulation of rapid NAT1 genotypes and smokers.


CONCLUSIONS
The present study demonstrates the association of PCA and MnSOD. Oxidative stress and cigarette smoking may play an important role in the carcinogenesis of the prostate in those who have MnSOD AA and rapid NAT1 genotypes.
Iguchi
Taro
T
Department of Urology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Sugita
Shozo
S
Wang
Ching Y
CY
Newman
Nancy B
NB
Nakatani
Tatsuya
T
Haas
Gabriel P
GP
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D012907:Smoking; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D007527:Isoenzymes; D013482:Superoxide Dismutase; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human