only were consistent, we present the more fully adjusted results to address the fact that farmers are exposed to many agents. To assess trends in dose–response patterns, we performed linear trend tests by assigning each exposure category the median value in that category and treating the variable as a continuous variable. To further examine the risk of prostate cancer, we obtained a parsimonious model by removing variables that did not alter point estimates by > 5%, leaving variables for age and state of residence in the model. We used an interaction term obtained by taking the product of family history of prostate cancer and category of lifetime exposure-days to eval- uate effect modification between phorate exposure and family history of prostate cancer. Results Table 1 displays selected characteristics of applicators by their level of exposure, with “lowest exposed” referring to those in the low- est exposed tertile of lifetime exposure-days, and “other exposed” referring to those in the remaining tertiles. Overall, those in the nonex- posed category tended to be less likely to report producing corn, slightly less likely to report family history of any cancer, and younger than those in either of the exposed categories. Additionally, compared with the exposed applicators, the nonexposed were also exposed to signiﬁcantly fewer of the pesticides that were assessed in the questionnaires. Finally, residents of North Carolina were more likely than resi- dents of Iowa to be nonexposed. These differ- ences between the nonexposed group and either of the two exposed groups suggest that the lowest exposed group may be the more appropriate reference group. Table 2 displays adjusted associations between selected cancer sites and phorate life- time exposure-days. Phorate use did not appear to be associated with the incidence of all cancers combined. For prostate and colon cancer, the results differed depending on the reference group. The risk estimates for both cancers increased monotonically with increas- ing exposure category relative to the lowest exposed, but the point estimates and linear trend tests were not signiﬁcant. However, the point estimates were not elevated compared with the nonexposed. Phorate use was not related to any other examined cancer. Because phorate use was uncommon in North Carolina, we repeated our analysis of all cancers combined, restricting the data to applicators from Iowa. The results were simi- lar to those presented above (not shown). Table 2. RRs (95% CIs) for selected cancers by phorate lifetime exposure-days among AHS (1993–1997) applicators, using nonexposed and lowest exposed applicators as the reference group. Cases (n) Nonexposed reference Lowest exposed reference p-Trend, p-value for trend test. Incidence RRs adjusted for age, state of residence, applicator type, education, family his- tory of site-speciﬁc cancer, smoking, and use of aldicarb, ethylene dibromide, aldrin, 2,4,5-TP, and butylate. aLifetime exposure-days = years of use × days of use per year. Environmental Health Perspectives • VOLUME 114 | NUMBER 8 | August 2006 Lifetime exposure-daysa All cancer 0 > 0–8.75 > 8.75–38.75 > 38.75–108.5 > 108.5 p-Trend Lymphohematopoietic cancer 0 > 0–8.75 > 8.75–38.75 > 38.75 p-Trend Colon cancer 0 > 0–8.75 > 8.75–38.75 > 38.75 p-Trend Lung cancer 0 > 0–8.75 > 8.75–38.75 > 38.75–108.5 > 108.5 p-Trend Prostate cancer 0 > 0–8.75 > 8.75–38.75 > 38.75–108.5 > 108.5 p-Trend 689 111 84 62 38 72 9 9 8 53 6 7 10 69 6 5 4 4 286 53 38 28 16 1.00 0.84 (0.68–1.04) 0.94 (0.74–1.19) 0.89 (0.68–1.17) 0.94 (0.67–1.33) 0.71 1.00 0.59 (0.20–1.12) 0.88 (0.40–2.03) 0.64 (0.52–2.17) 0.30 1.00 0.47 (0.20–1.13) 0.90 (0.40–2.03) 1.07 (0.49–2.52) 0.74 1.00 0.81 (0.34–1.96) 1.00 (0.39–2.61) 0.82 (0.29–2.37) 0.95 (0.31–2.94) 0.91 1.00 0.89 (0.65–1.21) 0.91 (0.64–1.29) 0.92 (0.62–1.38) 0.93 (0.55–1.57) 0.78 1.00 1.14 (0.85–1.53) 1.08 (0.78–1.49) 1.19 (0.79–1.78) 0.53 1.00 1.24 (0.48–3.22) 0.84 (0.30–2.33) 0.57 1.00 2.22 (0.72–6.83) 2.48 (0.84–7.36) 0.18 1.00 1.14 (0.34–3.84) 0.85 (0.22–3.23) 0.63 (0.14–2.86) 0.47 1.00 1.08 (0.71–1.66) 1.16 (0.73–1.86) 1.31 (0.72–2.37) 0.40 Occupational phorate exposure and cancer incidence They were not meaningfully different when we adjusted for lifetime exposure-days to all pesticides rather than the ﬁve most correlated pesticides (not shown). Finally, the results were also consistent when we examined days of use per year by years of use (not shown). Namely, we observed slightly elevated but insigniﬁcant point estimates for prostate and colon cancer, and no discernible pattern with any other examined cancer. Because of the large number of applicators excluded due to missing information on covariates, we repeated the analysis in Table 2 on all applicators without missing phorate exposure information by assigning the miss- ing covariates an unspecified category (not shown). The results of this analysis of 17,051 nonexposed and 6,488 exposed applicators did not substantially differ from the results presented above. Using the intensity-weighted exposure-days metric, though the number of cases was slightly reduced because individuals were missing data on intensity metric covariates, except for prostate cancer the results were not meaning- fully different from those presented above (not shown). Phorate use was not associated with all cancers combined. Colon cancer risk estimates were not elevated using the nonexposed refer- ence group, but compared with the lowest exposed, they increased monotonically with exposure category (RR in highest exposed = 1.81; 95% CI, 0.58–5.60). RRs for prostate cancer were uninﬂuenced by exposure category regardless of reference group. Phorate use was not associated with any other examined cancers. Although too few exposed melanoma cases (n = 14) prevented inclusion of results in tables, there were some interesting yet statisti- cally insigniﬁcant observations. In particular, melanoma risk estimates tended to increase with lifetime and intensity-weighted expo- sure-days category regardless of reference group. Relative to the unexposed, risk esti- mates were also elevated among low and high days of use per year, but only in applicators with many years of use. When prostate cancer risk was stratiﬁed by family history of prostate cancer, risk estimates did not increase across categories of lifetime exposure-days in the stratum of applicators reporting no family history (Table 3). However, in applicators with a family history, the risk estimates tended to increase. The RR in the highest compared to the lowest exposed was 1.91 (95% CI, 0.86–4.24). The interaction RR indicated that the risk associated with an increase in phorate exposure category was 1.53 (95% CI, 0.99–2.37) times higher in those with a family history of prostate cancer com- pared with those without. To account for latency of exposure, we repeated the analysis among applicators whose ﬁrst use of phorate was prior to 1980 (not shown). Too few 1207