Ide fonofos and known susceptibility loci in the 8q24 region and significant increased risks of prostate cancer, suggesting that variants identified from GWAS may interact with environmental factors [28]. With increasing information about the function of the 8q24 region in cancer development [29?1], this finding provides valuable information about how pesticide use might act to influence prostate cancer risk. In this study, we use newly genotyped data in 32 prostate GWAS SNPs to continue to explore possible SNP-pesticide interactions and risk of prostate cancer in 2,220 AHS subjects included in a nested case-control study.Materials and Methods Study populationThe AHS is a prospective cohort study that includes 55,747 male licensed pesticide applicators in Iowa and North Carolina,GWAS SNPs, Pesticides and Prostate CancerTable 1. Selected characteristics of prostate nested casecontrol participants.Cases Selected Characteristics All subjects Age (years) ,40 40?9 50?9 60?9 70 12 138 369 219 38 776 State of Residence Iowa North Carolina Applicator Type Autophagy Private Commercial 741 35 95.5 4.5 520 256 67.0 33.0 1.5 17.8 47.6 28.2 4.9 n 776 100.Controls n 1,444 100.0 Chi square pvalue17 273 673 4081.2 18.9 46.6 28.3 5.1 0.lost to follow-up at the time of case diagnosis, and had no previous cancer diagnosis except non-melanoma skin cancer. Based on these inclusion criteria, 841 cases (66 of total white cases in the cohort as of 2004) and 1,659 controls were identified (total N = 2,500). Due to genotyping space limitations 164 controls were excluded. Of the remaining samples, 108 were removed due to insufficient or poor DNA quality (N = 20; 14 cases, 6 controls) or ,90 completion rate (i.e. more than 10 of the SNP assays failed for a given sample, N = 88; 47 cases, 41 controls). We further identified 5 individuals who were suspected to be non-white (,80 European ancestry using STRUCTURE software [33] or significant deviation from the first two components in principal components Autophagy analysis [34]) leaving a final sample size of 776 cases and 1,444 controls. Participants provided written informed consent, and the study protocol was approved by the institutional review boards of the National Institutes of Health, the University of Iowa, and other contractors in compliance with all applicable requirements of the 23727046 United States.99168.6 31.4 0.Genotyping and Quality ControlThirty-two SNPs not 1326631 previously genotyped in the AHS but reported as susceptibility loci from GWAS of prostate cancer [17?27] were evaluated. Genotyping was performed at NCI’s Core Genotyping Facility (http://cgf.nci.nih.gov/operations/uniplexgenotyping.html) [35], using Applied Biosystems TaqManH SNP Genotyping Assays. SNPs with low completion rate (,90 of samples) were excluded (rs1465618 and rs4962416). The mean genotyping rate was 96 for the remaining 30 SNPs. No SNPs showed evidence of deviation from Hardy-Weinberg proportions given alpha = 0.05/30 = 0.0017 after Bonferroni correction. Blinded duplicate samples (5 ) were also included and concordance of these samples was 100 .1,36394.4 5.6 0.First-degree family history of prostate cancer No Yes Prostate Cancer Stage I ?Local II ?Regional III ?Distant IV ?Not staged Prostate Cancer Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Not graded 38 547 168 4 19 4.9 70.5 21.6 0.5 2.4 578 156 12 30 74.5 20.1 1.5 3.9 576 130 74.2 16.8 1,193 145 82.6 10.0 ,.Statistical AnalysisUnconditional logist.Ide fonofos and known susceptibility loci in the 8q24 region and significant increased risks of prostate cancer, suggesting that variants identified from GWAS may interact with environmental factors [28]. With increasing information about the function of the 8q24 region in cancer development [29?1], this finding provides valuable information about how pesticide use might act to influence prostate cancer risk. In this study, we use newly genotyped data in 32 prostate GWAS SNPs to continue to explore possible SNP-pesticide interactions and risk of prostate cancer in 2,220 AHS subjects included in a nested case-control study.Materials and Methods Study populationThe AHS is a prospective cohort study that includes 55,747 male licensed pesticide applicators in Iowa and North Carolina,GWAS SNPs, Pesticides and Prostate CancerTable 1. Selected characteristics of prostate nested casecontrol participants.Cases Selected Characteristics All subjects Age (years) ,40 40?9 50?9 60?9 70 12 138 369 219 38 776 State of Residence Iowa North Carolina Applicator Type Private Commercial 741 35 95.5 4.5 520 256 67.0 33.0 1.5 17.8 47.6 28.2 4.9 n 776 100.Controls n 1,444 100.0 Chi square pvalue17 273 673 4081.2 18.9 46.6 28.3 5.1 0.lost to follow-up at the time of case diagnosis, and had no previous cancer diagnosis except non-melanoma skin cancer. Based on these inclusion criteria, 841 cases (66 of total white cases in the cohort as of 2004) and 1,659 controls were identified (total N = 2,500). Due to genotyping space limitations 164 controls were excluded. Of the remaining samples, 108 were removed due to insufficient or poor DNA quality (N = 20; 14 cases, 6 controls) or ,90 completion rate (i.e. more than 10 of the SNP assays failed for a given sample, N = 88; 47 cases, 41 controls). We further identified 5 individuals who were suspected to be non-white (,80 European ancestry using STRUCTURE software [33] or significant deviation from the first two components in principal components analysis [34]) leaving a final sample size of 776 cases and 1,444 controls. Participants provided written informed consent, and the study protocol was approved by the institutional review boards of the National Institutes of Health, the University of Iowa, and other contractors in compliance with all applicable requirements of the 23727046 United States.99168.6 31.4 0.Genotyping and Quality ControlThirty-two SNPs not 1326631 previously genotyped in the AHS but reported as susceptibility loci from GWAS of prostate cancer [17?27] were evaluated. Genotyping was performed at NCI’s Core Genotyping Facility (http://cgf.nci.nih.gov/operations/uniplexgenotyping.html) [35], using Applied Biosystems TaqManH SNP Genotyping Assays. SNPs with low completion rate (,90 of samples) were excluded (rs1465618 and rs4962416). The mean genotyping rate was 96 for the remaining 30 SNPs. No SNPs showed evidence of deviation from Hardy-Weinberg proportions given alpha = 0.05/30 = 0.0017 after Bonferroni correction. Blinded duplicate samples (5 ) were also included and concordance of these samples was 100 .1,36394.4 5.6 0.First-degree family history of prostate cancer No Yes Prostate Cancer Stage I ?Local II ?Regional III ?Distant IV ?Not staged Prostate Cancer Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Not graded 38 547 168 4 19 4.9 70.5 21.6 0.5 2.4 578 156 12 30 74.5 20.1 1.5 3.9 576 130 74.2 16.8 1,193 145 82.6 10.0 ,.Statistical AnalysisUnconditional logist.