title: Influence of cytokine gene polymorphisms on the development of prostate cancer.
abstract: 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.
authors.affiliation: Department of Histocompatibility and Immunogenetics, Southampton University Hospitals NHS Trust, SO16 6YD, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: McCarron
authors.forename: Stephen
authors.initials: S
authors.lastname: Edwards
authors.forename: Philip R
authors.initials: PR
authors.lastname: Evans
authors.forename: Roz
authors.initials: R
authors.lastname: Gibbs
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: Anna
authors.initials: A
authors.lastname: Dowe
authors.forename: Christine
authors.initials: C
authors.lastname: Southgate
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: W Martin
authors.initials: WM
authors.lastname: Howell
mesh_terms: 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
chemical_list: 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