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

S. Lilly Zheng, Wennuan Liu, Fredrik Wiklund, Latchezar Dimitrov, Katarina Bälter, Jielin Sun, Hans Olov Adami, Jan Erik Johansson, Jishan Sun, Baoli Chang, Matthew Loza, Aubrey R. Turner, Eugene R. Bleecker, Deborah A. Meyers, John D. Carpten, David Duggan, William B. Isaacs, Jianfeng Xu, Henrik Grönberg

Research output: Contribution to journalArticlepeer-review

Abstract

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 MegAlleleTM 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 ∼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.

Original languageEnglish (US)
Pages (from-to)1556-1564
Number of pages9
JournalProstate
Volume66
Issue number14
DOIs
StatePublished - Oct 1 2006

Keywords

  • CIDEB
  • CRLF1
  • FCER2
  • Inflammation
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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