Interactions of cytokine gene polymorphisms in prostate cancer risk

• Published in: Carcinogenesis (New York) Vol. 29; no. 3; pp. 573 - 578
• Main Authors: Zabaleta, Jovanny, Lin, Hui-Yi, Sierra, Rosa A., Hall, M.Craig, Clark, Peter E., Sartor, Oliver A., Hu, Jennifer J., Ochoa, Augusto C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-03-2008; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Black or African American; Black People; Carcinogenesis, carcinogens and anticarcinogens; Case-Control Studies; Cytokines - genetics; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Multivariate Analysis; Nephrology. Urinary tract diseases; Polymorphism, Single Nucleotide; Prostatic Neoplasms - ethnology; Prostatic Neoplasms - genetics; Risk Factors; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; White People; Urinary system disease; Genetic variability; Prostate disease; Cytokine; Risk factor; Genotype; Risk; Malignant tumor; Male genital diseases; Prostate cancer; Epidemiology; Cancer
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/bgm277

Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case–control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)–logit models. African-Americans with the IL10−819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07–1.01], but subjects with the genotype combination of IL1B−511CT/TT and IL10−592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09–6.02). In Caucasians, higher CaP risk was associated with the IL10−1082AG/GG genotype (OR = 3.62, 95% CI = 1.42–9.28), the genotype combination of IL10−1082AA plus IL1B−31TT/TC (OR = 2.92, 95% CI = 1.13–7.55) and the genotype combination of TNF−238GG plus IL10−592AA (OR = 2.14, 95% CI = 1.05–4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk.