Polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk.
BACKGROUND
Presence of xenotropic murine leukemia virus-related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. This study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas.


METHODS
Cases (n = 193) were men, aged 40-80, diagnosed with prostate cancer in three 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, polymorphisms in COX-2 (rs689466) and IL-8 (rs4073) were not significantly associated with prostate cancer risk. However, apparent interactions were observed between these genetic variants and plasma antioxidants on the risk of this malignancy. The protective effect of the mutant allele of the COX-2 polymorphism was more pronounced among subjects with high plasma levels of beta-cryptoxanthin, lycopene, beta-carotene, or selenium (>or=median) [e.g., OR (95% CI): 0.37 (0.15, 0.86) (AG/GG vs. AA) for beta-cryptoxanthin]. Conversely, the promoting effect of the variant allele of the IL-8 polymorphism was more remarkable in subjects with low plasma levels of Lutein/zeaxanthin, beta-cryptoxanthin, and beta-carotene (<median) [e.g., OR (95% CI): 2.44 (1.08, 5.75) (AT/TT vs. AA) for beta-carotene].


CONCLUSIONS
We found that sequence variants in inflammatory genes interact with plasma antioxidants to modulate prostate cancer risk.
Zhang
Jianjun
J
Department of Public Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA. jz21@iupui.edu
Dhakal
Ishwori B
IB
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; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D012307:Risk Factors
D000975:Antioxidants; D016209:Interleukin-8; D051546:Cyclooxygenase 2