Influence of cytokine gene polymorphisms on the development of prostate cancer.
Polymorphisms in the promoter regions of cytokine genes may influence prostate cancer (PC) development via regulation of the antitumor immune response and/or pathways of tumor angiogenesis. PC patients (247) and 263 controls were genotyped for interleukin (IL)-1beta-511, IL-8-251, IL-10-1082, tumor necrosis factor-alpha-308, and vascular endothelial growth factor (VEGF)-1154 single nucleotide polymorphisms. Patient control comparisons revealed that IL-8 TT and VEGF AA genotypes were decreased in patients compared with controls [23.9 versus 32.3%; P = 0.04, odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.44-0.99 and 6.3 versus 12.9%; P = 0.01, OR = 0.45, 95% CI 0.24-0.86, respectively], whereas the IL-10 AA genotype was significantly increased in patients compared with controls (31.6 versus 20.6%; P = 0.01, OR = 1.78, 95% CI 1.14-2.77). Stratification according to prognostic indicators showed association between IL-8 genotype and log prostate-specific antigen level (P = 0.05). These results suggest that single nucleotide polymorphisms associated with differential production of IL-8, IL-10, and VEGF are risk factors for PC, possibly acting via their influence on angiogenesis.
McCarron
Sarah L
SL
Department of Histocompatibility and Immunogenetics, Southampton University Hospitals NHS Trust, SO16 6YD, United Kingdom.
Edwards
Stephen
S
Evans
Philip R
PR
Gibbs
Roz
R
Dearnaley
David P
DP
Dowe
Anna
A
Southgate
Christine
C
Easton
Douglas F
DF
Eeles
Rosalind A
RA
Howell
W Martin
WM
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D016228:Endothelial Growth Factors; D007378:Interleukins; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors