Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants.
OBJECTIVE
To investigate whether polymorphisms in genes involved in the repair of oxidative DNA damage, modulate, and/or interact with antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. Accumulating evidence indicates that oxidative stress plays a role in prostate carcinogenesis.


METHODS
Cases (n = 193) included men aged 40-80 years, diagnosed with prostate cancer in 3 major hospitals in 1998-2003, and controls (n = 197) were matched to cases by age, race, and county of residence.


RESULTS
After adjustment for confounders, subjects who were heterozygous or homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism appeared to experience a lower risk of prostate cancer than those who were homozygous for the wild-type allele (odds ratio [OR] (95% confidence interval [CI]): 0.72 (0.46-1.10)]. Conversely, a significant increased risk was observed for individuals who carried 1 or 2 copies of the variant allele of the XRCC1 Arg399Gln polymorphism, compared with those who only harbored the wild-type allele (OR [95% CI]: 1.56 [1.01-2.45]). The above-mentioned associations were generally more pronounced among subjects with low plasma carotenoids or alpha-tocopherol (<median). Among subjects who had low plasma levels of beta-cryptoxanthin (<73 microg/L), possession of at least 1 copy of the XRCC1 399Gln allele conferred a greater than 2-fold elevated risk (OR [95% CI]: 2.64 [1.40-5.07]).


CONCLUSIONS
Our study offers preliminary but intriguing data suggesting that variability in the capacity of repairing oxidative DNA damage influences susceptibility to prostate cancer and that these effects are modified by antioxidants.
Zhang
Jianjun
J
Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. jz21@iupui.edu
Dhakal
Ishwori B
IB
Greene
Graham
G
Lang
Nicholas P
NP
Kadlubar
Fred F
FF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000032:analysis*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
D000975:Antioxidants; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human