It has been suggested that NF-κB triggers both the onset and resolution of inflammation by governing the expression of genes essential in activating malignancy-promoting signaling pathways. Members of the NF-κB activation pathway include tumor necrosis factor (TNF), several interleukins (IL), TNF receptor associated factors (TRAFs), and toll-like receptors (TLR). These molecules are involved in cell proliferation, differentiation, apoptosis and response to proinflammatory cytokines and mediating the production of cytokines necessary for the development of effective immunity. Common single nucleotide polymorphisms (SNP) in TNF, IL, TRAF, TLR and the main units of NF-κB genes were assessed for the association with prostate cancer (PrCA) risk in a clinic-based study of Caucasian and African-American cases and controls. A total of 709 tagSNPs (with minor allele frequency > = 5% and r2>=0.8) in 54 genes were genotyped in 903 Caucasians (552 cases and 351 controls) and 174 African-Americans (74 cases and 100 controls) using a custom Illumina Infinium II ® assay. Logistic regression models were used to examine each tagSNP with PrCA (adjusting for age and family history of prostate cancer and using an additive model for the SNP). Empirical p-values were generated by permutation (using 10,000 replicates) to correct for multiple comparisons. Statistically significant associations were observed in Caucasians at the NFkBIL1 and IL1R1 genes. The strongest evidence for association came at a polymorphism in the promoter region of the NFkBIL1 gene (rs3219184) (OR = 0.51 [95% CI 0.35-0.74], p = 0.0005), and a polymorphism in the 3’ flanking region of the IL1R1 gene (rs3917332) (OR = 1.60 [95% CI 1.23-2.09], p = 0.0005). We conclude that common variations in NFkBIL1 and IL1R1 might play important roles in PrCA susceptibility.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2771. doi:10.1158/1538-7445.AM2011-2771