Age (within 5 years), ethnicity, and medical institution, who underwent standard annual

Age (within 5 years), ethnicity, and medical institution, who underwent standard annual exams at the major medical institutions in Cleveland, and who did not have a previous history of non-skin cancer. The PSA was measured and found elevated in two controls. Further investigations lead us to reclassify them as advanced cases of prostate cancer, leaving us with a total ofInnate Immunity Inflammation in Prostate CancerTable 1. Study characteristics of the advanced prostate cancer cases and controls.Cases (n = 494) Age (year), mean (SD) Ethnicity, n ( ) African American Caucasian Prostate cancer in first degree relative, n ( )b Negative Positive PSA at diagnosis (ng/mL), mean (SD) Categories of PSA at diagnosis, n ( ) ,4.0 4.0?.9 10?9.9 20?9.9 .50 Gleason score, n ( ) #6 3+4 4+3 or 8 Clinical stage, n ( ) T1 T2a-T2b T2c T3a bControls (n = 536) (8.34) 65.85 (8.54)P-value of heterogeneitya 0.65.90(18.2) (81.8)104(19.4) (80.6)0.381 112 14.(77.3) (22.7) (27.67)472 59 1.(88.9) (11.1) (1.71),2610216 ,25 249 152 53(5.1) (50.4) (30.8) (10.7) (3.0)??????????74 217(15.0) (43.9) 15481974 (41.1)??????306 127 15(64.7) (26.8) (3.2) (5.3)????????P-values obtained using either a Student t-test (quantitative coding) or a Chi-square test (qualitative coding). The sum of all categories does not add to the total due to missing data. doi:10.1371/journal.pone.0051680.tbadvanced prostate cancer cases and 536 controls used here in our analyses. Approval for this study was obtained from the University Hospitals of Cleveland Institutional Review Board and the Cleveland Clinic Foundation Institutional Review Board, and written informed consent was obtained from all study participants. More details about this study population have been previously described [27,29,32,33,34,35,36].SNP Selection, Genotyping and Quality ControlWe selected for study 46 candidate genes coding for proteins involved in innate immunity and inflammation, and further grouped these into 6 relevant biological sub-pathways using a previously proposed and published classification [37]. These subpathways were: 1) cytokine signaling (26 genes), 2) eicosanoid signaling (1 gene, i.e. COX-2), 3) extracellular pattern recognition (8 genes), 4) intracellular antiviral Tetracosactrin molecules (4 genes), 5) nuclear kappa-light chain-enhancer or activated B cell (NFKB) signaling (5 genes), and 6) selenoproteins (2 genes). The genes SELS and SEP15 coding for selenoproteins were included because of their potential role in the control of the inflammatory response through regulation of cytokine production [38]. All SNPs located within and 2 kb upstream and 1 kb downstream of the sequence of the 46 candidate genes were identified through the International HapMap Project (www. hapmap.org) and the Genome Variation Server (SeattleSNPs) (http://gvs.gs.washington.edu/). Then, tagging SNPs were selected using the multimarker test criteria in the Tagger software program [39] to capture all common SNPs (minor allele frequency, MAF .0.05) with an r2 0.8 across each candidate gene among European ancestry populations, forcing SNPs that are missense, non-synonymous and previously associated with prostate cancer to be included. Only one missense SNP was included for the genes TLR3 and IL6R. Moreover, 39 ancestry informative markers (AIMs) [40] were genotyped and principal component analysis was used to MedChemExpress JSI124 estimate genetic ancestry and account for population stratification [41]. The first principal component of this analysis distinguished African Am.Age (within 5 years), ethnicity, and medical institution, who underwent standard annual exams at the major medical institutions in Cleveland, and who did not have a previous history of non-skin cancer. The PSA was measured and found elevated in two controls. Further investigations lead us to reclassify them as advanced cases of prostate cancer, leaving us with a total ofInnate Immunity Inflammation in Prostate CancerTable 1. Study characteristics of the advanced prostate cancer cases and controls.Cases (n = 494) Age (year), mean (SD) Ethnicity, n ( ) African American Caucasian Prostate cancer in first degree relative, n ( )b Negative Positive PSA at diagnosis (ng/mL), mean (SD) Categories of PSA at diagnosis, n ( ) ,4.0 4.0?.9 10?9.9 20?9.9 .50 Gleason score, n ( ) #6 3+4 4+3 or 8 Clinical stage, n ( ) T1 T2a-T2b T2c T3a bControls (n = 536) (8.34) 65.85 (8.54)P-value of heterogeneitya 0.65.90(18.2) (81.8)104(19.4) (80.6)0.381 112 14.(77.3) (22.7) (27.67)472 59 1.(88.9) (11.1) (1.71),2610216 ,25 249 152 53(5.1) (50.4) (30.8) (10.7) (3.0)??????????74 217(15.0) (43.9) 15481974 (41.1)??????306 127 15(64.7) (26.8) (3.2) (5.3)????????P-values obtained using either a Student t-test (quantitative coding) or a Chi-square test (qualitative coding). The sum of all categories does not add to the total due to missing data. doi:10.1371/journal.pone.0051680.tbadvanced prostate cancer cases and 536 controls used here in our analyses. Approval for this study was obtained from the University Hospitals of Cleveland Institutional Review Board and the Cleveland Clinic Foundation Institutional Review Board, and written informed consent was obtained from all study participants. More details about this study population have been previously described [27,29,32,33,34,35,36].SNP Selection, Genotyping and Quality ControlWe selected for study 46 candidate genes coding for proteins involved in innate immunity and inflammation, and further grouped these into 6 relevant biological sub-pathways using a previously proposed and published classification [37]. These subpathways were: 1) cytokine signaling (26 genes), 2) eicosanoid signaling (1 gene, i.e. COX-2), 3) extracellular pattern recognition (8 genes), 4) intracellular antiviral molecules (4 genes), 5) nuclear kappa-light chain-enhancer or activated B cell (NFKB) signaling (5 genes), and 6) selenoproteins (2 genes). The genes SELS and SEP15 coding for selenoproteins were included because of their potential role in the control of the inflammatory response through regulation of cytokine production [38]. All SNPs located within and 2 kb upstream and 1 kb downstream of the sequence of the 46 candidate genes were identified through the International HapMap Project (www. hapmap.org) and the Genome Variation Server (SeattleSNPs) (http://gvs.gs.washington.edu/). Then, tagging SNPs were selected using the multimarker test criteria in the Tagger software program [39] to capture all common SNPs (minor allele frequency, MAF .0.05) with an r2 0.8 across each candidate gene among European ancestry populations, forcing SNPs that are missense, non-synonymous and previously associated with prostate cancer to be included. Only one missense SNP was included for the genes TLR3 and IL6R. Moreover, 39 ancestry informative markers (AIMs) [40] were genotyped and principal component analysis was used to estimate genetic ancestry and account for population stratification [41]. The first principal component of this analysis distinguished African Am.