Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

A comprehensive association study for genes in inflammation pathway provides support for their roles in prostate cancer risk in the CAPS study.

Zheng SL, Liu W, Wiklund F, Dimitrov L, Bälter K, Sun J, Adami HO, Johansson JE, Sun J, Chang B, Loza M, Turner AR, Bleecker ER, Meyers DA, Carpten JD, Duggan D, Isaacs WB, Xu J, Grönberg H

Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

BACKGROUND: Recently identified associations of prostate cancer risk with several genes involved in innate immunity support a role of inflammation in the etiology of prostate cancer. Considering inflammation is regulated by a complex system of gene products, we hypothesize sequence variants in many other genes of this pathway are associated with prostate cancer. METHODS: We evaluated 9,275 SNPs in 1,086 genes of the inflammation pathway using a MegAllele genotyping system among 200 familial cases and 200 unaffected controls selected from a large Swedish case-control population (CAPS). RESULTS: We found that significantly more than the expected numbers of SNPs were significant at a nominal P-value of 0.01, 0.05, and 0.1, providing overall support for our hypothesis. The excess was largest when using a more liberal nominal P-value (0.1); we observed 992 significant SNPs compared with the 854 significant SNPs expected by chance, and this difference was significant based on a permutation test (P = 0.0025). We also began the effort of differentiating true associated SNPs by selecting a small subset of significant SNPs (N = 26) and genotyped these in an independent sample of approximately 1,900 CAPS1 subjects. We were able to confirm 3 of these 26 SNPs. It is expected that many more true associated SNPs will be confirmed among the 992 significant SNPs identified in our pathway screen. CONCLUSIONS: Our study provides the first objective support for an association between prostate cancer and multiple modest-effect genes in inflammatory pathways.

Published 4 September 2006 in Prostate, 66(14): 1556-64.
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