Carcinogenesis Advance Access originally published online on January 3, 2008
Carcinogenesis 2008 29(3):573-578; doi:10.1093/carcin/bgm277
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Interactions of cytokine gene polymorphisms in prostate cancer risk
1 Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 455, New Orleans, LA 70112, USA
2 Medical Statistics Section, University of Alabama at Birmingham, Birmingham, AL 35294, USA
3 Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
4 Department of Urology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
5 Department of Urologic Surgery and Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
6 Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA 02115, USA and
7 Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami School of Medicine, Miami, FL 33136, USA
8 Present address: Piedmont Urological Associates, High Point, NC 27262, USA
* To whom correspondence should be addressed. Tel: +(504) 599 0920; Fax: +(504) 599 0911; Email: jzabal{at}lsuhsc.edu
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.
Abbreviations: BPH, benign prostatic hyperplasia; CaP, prostate cancer; CI, confidence interval; HWE, Hardy–Weinberg equilibrium; IL, interleukin; MARS, multivariate adaptive regression spline; OR, odds ratio; SNP, single-nucleotide polymorphism; TNF, tumor necrosis factor
Received August 1, 2007; revised November 26, 2007; accepted November 27, 2007.