Ic regression was used to estimate odds ratios (ORs) and 95 confidence intervals (CIs) for the association between SNPs and prostate cancer and the interaction between SNPs and pesticide use with prostate cancer risk. For SNP associations, genotypes were coded as counts of the risk allele assuming a log-additive model 
and models were adjusted for age (10 yr-intervals) and state (Iowa or North Carolina). Information on lifetime use of 50 pesticides was captured in two selfadministered questionnaires completed during cohort enrollment. All nested case-control study participants completed the first (enrollment) questionnaire, which inquired about ever/never use of the 50 pesticides, as well as duration and frequency of use for a subset of 22 of the pesticides, while 1,439 of these men (60.4 of cases and 67.2 of controls), completed the second (take-home) questionnaire, which inquired about use of the remaining 28 pesticides. Pesticides with a prevalence of use less than 5 in the current nested case-control subgroup were excluded leaving 45 pesticides for analysis (17 herbicides, 21 insecticides, 2 fumigants, and 5 fungicides); a list of all 45 pesticides and their prevalence of use is presented in Table S1. Cumulative lifetime exposure to each pesticide was assessed by intensity-weighted lifetime exposure days and categorized into three groups (non-exposed, low, and high, with low and high divided at the median among controls for each pesticide). SNP-pesticide interactions, adjusted for age and state, were examined in a multiplicative model using the three-level pesticide variable and assuming the dominant genetic model for SNPs. The 58-49-1 P-value (1 df) for each SNP-pesticide interaction was computed by comparing nested models with and without the cross-product terms using a likelihood ratio test. SNP-pesticide combinations with a P-interaction,0.05 and a significantdoi:10.1371/journal.pone.0058195.trecruited from 1993 through 1997 [32]. During a follow-up interview conducted in 1999?003, applicators were asked for a mouthwash rinse sample to provide DNA from buccal cells. Approximately 72 of all 
applicators who completed the followup interview returned a buccal sample. In addition, applicators with incident prostate cancer who had not returned a sample at follow-up were asked separately to provide one, 23727046 with 307/561 (55 ) returning a sample. White male pesticide applicators diagnosed with incident prostate cancer between 1993 and 2004 were included in the current nested case-control study. Eligibility, inclusion and exclusion criteria have been previously described [28]. Briefly, cancer cases were coded using the International Classification of Diseases for Oncology, 2nd edition, and stage (local, regional, distant, unstaged) and grade (well differentiated, moderately differentiated, poorly differentiated, undifferentiated, missing) were abstracted by the state cancer registries in Iowa and North Carolina. Eligible controls were frequency matched 2:1 to cases by date of birth (+/2 1 year). Controls were white, male applicators who provided buccal cell material, were alive and notGWAS SNPs, Pesticides and Prostate CancerTable 2. Risk of prostate cancer in the AHS for previously reported susceptibility loci identified from genome wide association studies of prostate cancer.Region 2p15 2p15 2p21 2q31 2q37 3p11 3p12 3q21 4q22 4q22 4q24 6q25 7p15 7q21 8q21 8q24 8q24 8p21 8p21 10q11 10q26 11q13 11p15 12q13 17q12 17q24 19qSNP rs721048 Fruquintinib rs2710647 r.Ic regression was used to estimate odds ratios (ORs) and 95 confidence intervals (CIs) for the association between SNPs and prostate cancer and the interaction between SNPs and pesticide use with prostate cancer risk. For SNP associations, genotypes were coded as counts of the risk allele assuming a log-additive model and models were adjusted for age (10 yr-intervals) and state (Iowa or North Carolina). Information on lifetime use of 50 pesticides was captured in two selfadministered questionnaires completed during cohort enrollment. All nested case-control study participants completed the first (enrollment) questionnaire, which inquired about ever/never use of the 50 pesticides, as well as duration and frequency of use for a subset of 22 of the pesticides, while 1,439 of these men (60.4 of cases and 67.2 of controls), completed the second (take-home) questionnaire, which inquired about use of the remaining 28 pesticides. Pesticides with a prevalence of use less than 5 in the current nested case-control subgroup were excluded leaving 45 pesticides for analysis (17 herbicides, 21 insecticides, 2 fumigants, and 5 fungicides); a list of all 45 pesticides and their prevalence of use is presented in Table S1. Cumulative lifetime exposure to each pesticide was assessed by intensity-weighted lifetime exposure days and categorized into three groups (non-exposed, low, and high, with low and high divided at the median among controls for each pesticide). SNP-pesticide interactions, adjusted for age and state, were examined in a multiplicative model using the three-level pesticide variable and assuming the dominant genetic model for SNPs. The P-value (1 df) for each SNP-pesticide interaction was computed by comparing nested models with and without the cross-product terms using a likelihood ratio test. SNP-pesticide combinations with a P-interaction,0.05 and a significantdoi:10.1371/journal.pone.0058195.trecruited from 1993 through 1997 [32]. During a follow-up interview conducted in 1999?003, applicators were asked for a mouthwash rinse sample to provide DNA from buccal cells. Approximately 72 of all applicators who completed the followup interview returned a buccal sample. In addition, applicators with incident prostate cancer who had not returned a sample at follow-up were asked separately to provide one, 23727046 with 307/561 (55 ) returning a sample. White male pesticide applicators diagnosed with incident prostate cancer between 1993 and 2004 were included in the current nested case-control study. Eligibility, inclusion and exclusion criteria have been previously described [28]. Briefly, cancer cases were coded using the International Classification of Diseases for Oncology, 2nd edition, and stage (local, regional, distant, unstaged) and grade (well differentiated, moderately differentiated, poorly differentiated, undifferentiated, missing) were abstracted by the state cancer registries in Iowa and North Carolina. Eligible controls were frequency matched 2:1 to cases by date of birth (+/2 1 year). Controls were white, male applicators who provided buccal cell material, were alive and notGWAS SNPs, Pesticides and Prostate CancerTable 2. Risk of prostate cancer in the AHS for previously reported susceptibility loci identified from genome wide association studies of prostate cancer.Region 2p15 2p15 2p21 2q31 2q37 3p11 3p12 3q21 4q22 4q22 4q24 6q25 7p15 7q21 8q21 8q24 8q24 8p21 8p21 10q11 10q26 11q13 11p15 12q13 17q12 17q24 19qSNP rs721048 rs2710647 r.