A comprehensive association study for genes in inflammation pathway provides support for their roles in prostate cancer risk in the CAPS study.
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.
Zheng
S Lilly
SL
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Liu
Wennuan
W
Wiklund
Fredrik
F
Dimitrov
Latchezar
L
Bälter
Katarina
K
Sun
Jielin
J
Adami
Hans-Olov
HO
Johansson
Jan-Erik
JE
Sun
Jishan
J
Chang
Baoli
B
Loza
Matthew
M
Turner
Aubrey R
AR
Bleecker
Eugene R
ER
Meyers
Deborah A
DA
Carpten
John D
JD
Duggan
David
D
Isaacs
William B
WB
Xu
Jianfeng
J
Grönberg
Henrik
H
D000368:Aged; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D011472:Prostatitis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology