DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population.
BACKGROUND
Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer.


METHODS
We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.


RESULTS
The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12-3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36-3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39-5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21-0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14-0.98; p = 0.05) among smokers.


CONCLUSIONS
It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.
Arizono
Katsuyuki
K
Department of Public Health, Faculty of Medicine, University of Miyazaki, 5200 Kihara Kiyotake, Miyazaki, 889-1692 Japan.
Osada
Yukio
Y
Kuroda
Yoshiki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D015984:Causality; D015897:Comorbidity; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human