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A comprehensive association study for genes in inflammation pathway provides support for their roles in prostate cancer risk in the CAPS study
Author(s) -
Zheng S. Lilly,
Liu Wennuan,
Wiklund Fredrik,
Dimitrov Latchezar,
Bälter Katarina,
Sun Jielin,
Adami HansOlov,
Johansson JanErik,
Sun Jishan,
Chang Baoli,
Loza Matthew,
Turner Aubrey R.,
Bleecker Eugene R.,
Meyers Deborah A.,
Carpten John D.,
Duggan David,
Isaacs William B.,
Xu Jianfeng,
Grönberg Henrik
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20496
Subject(s) - prostate cancer , medicine , inflammation , prostate , gene , cancer , association (psychology) , oncology , bioinformatics , biology , genetics , psychology , psychotherapist
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. Prostate 66: 1556–1564, 2006. © 2006 Wiley‐Liss, Inc.