Carcinogenesis Advance Access published online on January 3, 2008
Carcinogenesis, 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, New Orleans, LA 70112
2 Medical Statistics Section, University of Alabama at Birmingham, Birmingham, AL 35294
3 Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70112
4 Department of Urology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157
5 Department of Urologic Surgery and Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232
6 Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA 02115
7 Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami School of Medicine, Miami, FL 33136
Corresponding author: Jovanny Zabaleta, 533 Bolivar St, CSRB 455, New Orleans, LA 70112, 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 9 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 (OR=0.27, 95%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 IL-101082AA 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.
Key Words: Prostate cancer • Inflammation • SNPs • race/ethnicity • MARS
* Current address: Piedmont Urological Associates, High Point, NC 27262
Received August 1, 2007; revised November 26, 2007; accepted November 27, 2007.