S1465618{ rs12621278 rs2292884 rs7629490 rs2660753 rs4857841 rs12500426 rs17021918 rs7679673 rs9364554 rs10486567 rs6465657 rs4961199 rs16901979 AKT inhibitor 2 rs7841060 rs1512268 rs13264338 surrogate for rs2928679 rs10993994 rs4962416{ rs10896449 rs7127900 rs902774 rs4430796 rs1859962 rs17632542 rs266849 rsKnown gene/region EHBP1 EHBP1 THADA ITGA6 MLPH Intergenic Intergenic EEFSEC PDLIM5 PDLIM5 TET2, PP2A SLC22A3 JAZF1 LMTK2 CPNE3 Intergenic, HapC Intergenic, Region2 NKX3.1 SLC25A37 MSMB CTBP2 Intergenic IGF2, IGF2AS, INS, TH KRT8, EIF4B, TENC1 HNF1B Intergenic KLKRisk Allele A C ?A G T T A C C C T 25033180 C C C T G A C T ?G T T T G T A GRAF* 0.17 0.53 ?0.94 0.23 0.34 0.10 0.28 0.56 0.64 0.62 0.60 0.77 0.45 0.84 0.03 0.20 0.43 0.44 0.31 ?0.52 0.19 0.14 0.51 0.46 0.91 0.79 0.84 0.49 0.77 0.OR**95 CI 1.20 (1.00, 1.45) 1.24 (1.07, 1.43) ?1.06 (0.78, 1.43) 1.17 (0.99, 1.37) 1.05 (0.90, 1.22) 1.05 (0.83, 1.32) 1.13 (0.97, 1.31) 1.09 (0.94, 1.25) 1.03 (0.89, 1.18) 1.10 (0.96, 1.28) 1.11 (0.95, 1.29) 1.20 (1.01, 1.43) 1.13 (0.98, 1.31) 1.01 (0.84, 1.23) 1.60 (1.13, 2.28) 1.26 (1.06, 1.48) 1.14 (0.99, 1.32) 1.10 (0.97, 1.27) 1.30 (1.13, 1.50) ?1.20 (1.04, 1.38) 1.10 (0.92, 1.31) 1.29 (1.07, 1.56) 1.19 (1.06, 1.35) 1.25 (1.09, 1.45) 1.38 (1.09, 1.74) 1.23 (1.05, 1.44) 1.19 (1.00, 1.42) 1.26 (1.09, 1.45) 1.04 (0.88, 1.23) 1.12 (0.92, 1.38)P-trend 0.051 0.004 ?0.714 0.061 0.560 0.704 0.126 0.258 0.742 0.180 0.180 0.036 0.088 0.909 0.009 0.007 0.069 0.143 0.0002 ?0.012 0.289 0.007 0.005 0.002 0.007 0.013 0.051 0.002 0.661 0.22q13 22q13 Xprs5759167 rs600173 surrogate for rs9623117 rsTTLL1, BIK TNRC6B NUDT10, NUDTC T GSingle Nucleotide Polymorphism (SNP); Odds Ratio (OR); Confidence Interval (CI); Agricultural Health Study (AHS). *Risk Allele Frequency (RAF) among controls. ** OR per risk allele assuming a log-additive model. Adjusted for age and state. { Completion rate ,90 . rs600173-rs9623117 r2 = 1.0, rs13264338-rs2928679 r2 = 0.96. doi:10.1371/journal.pone.0058195.tincreased risk (a = 0.05) of prostate cancer following a monotonic pattern with increasing pesticide exposure in one genotype group and no significant association in the other group are presented. We also evaluated pesticide interactions with a cumulative score variable (continuous and categorical) by coding genotypes as zero, one, or two risk alleles to assess the contribution of multiple independent SNPs (n = 26, Gracillin web including those from 8q24 [28]) 1326631 and prostate cancer risk. All P-values are two-sided and all analyses were performed using AHS data release version P1REL0712.04. We applied the false discovery rate (FDR) (Benjamini ?Hochberg adjustment) method to account for the expected proportion of false discoveries. FDR values were calculated separately for each pesticide from the results of 30 tests (i.e., total number of SNPs evaluated) in the evaluation of the associationbetween each SNP-pesticide interaction and the risk of prostate cancer. Interactions were deemed noteworthy at an FDR = 0.20 level.ResultsApplicators in the current study were representative of applicators in the larger cohort with respect to a variety of demographic characteristics [28]. Also, cases were similar in age, state of residence, and applicator type to controls in the study but had a higher proportion of first-degree relatives with a family history of prostate cancer compared with controls (16.7 versus 10.0 , Table 1). All observed associations for the 30 SNPs and prostate cancer were in the same direction as reported in GWAS.S1465618{ rs12621278 rs2292884 rs7629490 rs2660753 rs4857841 rs12500426 rs17021918 rs7679673 rs9364554 rs10486567 rs6465657 rs4961199 rs16901979 rs7841060 rs1512268 rs13264338 surrogate for rs2928679 rs10993994 rs4962416{ rs10896449 rs7127900 rs902774 rs4430796 rs1859962 rs17632542 rs266849 rsKnown gene/region EHBP1 EHBP1 THADA ITGA6 MLPH Intergenic Intergenic EEFSEC PDLIM5 PDLIM5 TET2, PP2A SLC22A3 JAZF1 LMTK2 CPNE3 Intergenic, HapC Intergenic, Region2 NKX3.1 SLC25A37 MSMB CTBP2 Intergenic IGF2, IGF2AS, INS, TH KRT8, EIF4B, TENC1 HNF1B Intergenic KLKRisk Allele A C ?A G T T A C C C T 25033180 C C C T G A C T ?G T T T G T A GRAF* 0.17 0.53 ?0.94 0.23 0.34 0.10 0.28 0.56 0.64 0.62 0.60 0.77 0.45 0.84 0.03 0.20 0.43 0.44 0.31 ?0.52 0.19 0.14 0.51 0.46 0.91 0.79 0.84 0.49 0.77 0.OR**95 CI 1.20 (1.00, 1.45) 1.24 (1.07, 1.43) ?1.06 (0.78, 1.43) 1.17 (0.99, 1.37) 1.05 (0.90, 1.22) 1.05 (0.83, 1.32) 1.13 (0.97, 1.31) 1.09 (0.94, 1.25) 1.03 (0.89, 1.18) 1.10 (0.96, 1.28) 1.11 (0.95, 1.29) 1.20 (1.01, 1.43) 1.13 (0.98, 1.31) 1.01 (0.84, 1.23) 1.60 (1.13, 2.28) 1.26 (1.06, 1.48) 1.14 (0.99, 1.32) 1.10 (0.97, 1.27) 1.30 (1.13, 1.50) ?1.20 (1.04, 1.38) 1.10 (0.92, 1.31) 1.29 (1.07, 1.56) 1.19 (1.06, 1.35) 1.25 (1.09, 1.45) 1.38 (1.09, 1.74) 1.23 (1.05, 1.44) 1.19 (1.00, 1.42) 1.26 (1.09, 1.45) 1.04 (0.88, 1.23) 1.12 (0.92, 1.38)P-trend 0.051 0.004 ?0.714 0.061 0.560 0.704 0.126 0.258 0.742 0.180 0.180 0.036 0.088 0.909 0.009 0.007 0.069 0.143 0.0002 ?0.012 0.289 0.007 0.005 0.002 0.007 0.013 0.051 0.002 0.661 0.22q13 22q13 Xprs5759167 rs600173 surrogate for rs9623117 rsTTLL1, BIK TNRC6B NUDT10, NUDTC T GSingle Nucleotide Polymorphism (SNP); Odds Ratio (OR); Confidence Interval (CI); Agricultural Health Study (AHS). *Risk Allele Frequency (RAF) among controls. ** OR per risk allele assuming a log-additive model. Adjusted for age and state. { Completion rate ,90 . rs600173-rs9623117 r2 = 1.0, rs13264338-rs2928679 r2 = 0.96. doi:10.1371/journal.pone.0058195.tincreased risk (a = 0.05) of prostate cancer following a monotonic pattern with increasing pesticide exposure in one genotype group and no significant association in the other group are presented. We also evaluated pesticide interactions with a cumulative score variable (continuous and categorical) by coding genotypes as zero, one, or two risk alleles to assess the contribution of multiple independent SNPs (n = 26, including those from 8q24 [28]) 1326631 and prostate cancer risk. All P-values are two-sided and all analyses were performed using AHS data release version P1REL0712.04. We applied the false discovery rate (FDR) (Benjamini ?Hochberg adjustment) method to account for the expected proportion of false discoveries. FDR values were calculated separately for each pesticide from the results of 30 tests (i.e., total number of SNPs evaluated) in the evaluation of the associationbetween each SNP-pesticide interaction and the risk of prostate cancer. Interactions were deemed noteworthy at an FDR = 0.20 level.ResultsApplicators in the current study were representative of applicators in the larger cohort with respect to a variety of demographic characteristics [28]. Also, cases were similar in age, state of residence, and applicator type to controls in the study but had a higher proportion of first-degree relatives with a family history of prostate cancer compared with controls (16.7 versus 10.0 , Table 1). All observed associations for the 30 SNPs and prostate cancer were in the same direction as reported in GWAS.
