11,916,244 acres in Arizona. On average, approximately 32% of the total county acreage was cropland used for farming. There was quite a range of percent cropland among the study registries, with Arizona having the least average amount of cropland per county (1.8%) and Iowa averaging the most (74.7%). There were slightly more males than females among both the at-risk population and the cancer cases (Table 2). The children in the at-risk population were approximately evenly divided among 0–4 (32%), 5–9 (34%), and 10–14 (34%) years of age. In contrast, cancer cases were younger, with 45% of the total cases being < 5 years of age. The distribution of the at-risk population and the total cancer cases, leukemia cases, and central nervous system cases by county percent cropland was approximately equivalent, with about 70% residing in coun- ties with the lowest level of agricultural activity. When only total cancers as a group were considered, no association was seen for percent cropland either for the medium or the high levels of agricultural activity (Table 3). In con- trast, many speciﬁc cancer sites had statistically significantly elevated risk estimates for the medium agricultural activity category, includ- ing Hodgkin lymphoma (OR = 1.3; 95% CI, 1.1–1.5), Wilms’ tumor (OR = 1.3; 95% CI, 1.1–1.5), renal carcinomas (OR = 2.3; 95% CI, 1.3–4.2), hepatoblastoma (OR = 1.7; 95% CI, 1.3–2.3), Ewing’s sarcoma (OR = 1.8; 95% CI, 1.4–2.3), rhabdomyosarcomas (OR = 1.5; 95% CI, 1.2–1.7), thyroid carcinomas (OR = 1.8; 95% CI, 1.3–2.4), and malignant melanoma (OR = 1.6; 95% CI, 1.1–2.2). For the high exposure category (≥ 60% of the total county acreage devoted to farming), statisti- cally signiﬁcantly elevated ORs were seen for every cancer site examined, with many risk estimates showing two or more times the risk for childhood cancers when compared with the low level of agricultural activity. Additionally, there was a remarkably consis- tent indication of a possible dose–response effect when comparing risk estimates for the medium exposure category to the high. As with the all-ages estimates, we observed no association at either exposure level for total childhood cancers when risk was examined separately for infants < 1 year of age or for 5-year age groups (i.e., 1–4, 5–9, and 10–14 years of age) (Table 4). Risk estimates for can- cer subgroups generally mirrored that seen in the all-ages ORs, with statistically signiﬁcantly increased risk seen predominantly in the high- exposure category for each age group. There generally was no clear pattern of risk associ- ated with specific age groups for any of the individual cancers evaluated, perhaps except for neuroblastomas, where risk was elevated primarily for tumors diagnosed before 5 years of age, and lymphomas, osteosarcomas, and thyroid cancers, where risk was statistically Environmental Health Perspectives • VOLUME 116 | NUMBER 4 | April 2008 Leukemia [cases (%)] 3,354 (54) 2,814 (46) 321 (5) 2,944 (48) 1,689 (27) 1,214 (20) 4,341 (70) 1,357 (22) 470 (8) No. 1,598 470 387 66 155 58 60 348 184 69 121 118 45 102 96 5 23 21 84 44 33 109 59 57 77 26 25 7 CNS [cases (%)] 2,334 (54) 1,984 (46) 289 (7) 1,310 (30) 1,491 (35) 1,228 (28) 2,995 (69) 975 (23) 348 (8) OR (95% CI 1.0 (1.0–1.1) 1.2 (1.1–1.3) 1.3 (1.1–1.4) 1.8 (1.4–2.3) 1.4 (1.2–1.7) 2.1 (1.6–2.7) 2.1 (1.6–2.8) 1.3 (1.1–1.4) 1.5 (1.3–1.7) 1.9 (1.5–2.4) 1.7 (1.4–2.1) 1.8 (1.5–2.1) 2.6 (1.9–3.5) 2.1 (1.7–2.6) 2.1 (1.7–2.7) 3.3 (1.3–8.3) 3.3 (2.1–5.0) 4.0 (2.5–6.3) 2.3 (1.8–2.9) 2.7 (2.0–3.6) 4.3 (3.0–6.2) 1.7 (1.4–2.0) 2.5 (1.9–3.3) 2.3 (1.8–3.1) 2.2 (1.8–2.8) 3.0 (2.0–4.6) 4.6 (3.0–7.0) 11.2 (5.1–24.4) 561 significantly elevated only among the oldest ages. The majority of statistically significant ORs indicated a two-fold or greater risk for residence at diagnosis in exposed counties. We observed a variety of patterns when we evaluated six individual crops for childhood cancer risk (Table 5). We found no statistically significant associations for any of the child- hood cancers evaluated for residence at diagno- sis in a county with barley crops, and only negative associations reached statistical signiﬁ- cance for wheat production areas (hepatoblas- toma, Ewing’s sarcoma, thyroid carcinomas, malignant melanomas, and other and unspeci- fied cancers). Increased risk for cotton crops was seen only for renal carcinomas (OR = 6.9; Agricultural pesticides and childhood cancers 95% CI, 1.4–34.0). There were indications of increased risk for speciﬁc cancer sites with resi- dence in counties planted in corn, oats, and soybeans. No childhood cancers had an increased risk that was associated with corn only. Those cancers associated with increased risk for oat crops only included primitive neu- roectodermal tumors (OR = 1.5; 95% CI, 1.1–2.0), Ewing’s sarcoma (OR = 2.3; 95% CI, 1.4–3.7), germ cell tumors (OR = 2.6; 95% CI, 1.6–4.0), thyroid tumors (OR = 2.0; 95% CI, 1.2–3.4), and malignant melanoma (OR = 2.4; 95% CI, 1.3–4.5). Those cancers associated with increased risk for soybean production included only acute myeloid leukemias (OR = 1.4; 95% CI, 1.1–1.7), Table 2. Distribution of total childhood, leukemia, and central nervous system (CNS) cancer cases and at-risk population by sex, age, and percent cropland for study area, NAACCR 1995–2001. Characteristic Sex Male Female Age group (years) 0 1–4 5–9 10–14 County percent cropland < 20 20 to < 60 ≥ 60 At-risk population [no. (%)] 71,321,275 (51) 67,914,027 (49) 8,838,525 (6) 35,861,584 (26) 47,188,891 (34) 47,346,302 (34) 97,330,441 (70) 31,217,835 (22) 10,687,026 (8) All cancers [cases (%)] 10,856 (54) 9,378 (46) 2,095 (10) 7,123 (35) 5,195 (26) 5,821 (29) 14,160 (70) 4,476 (22) 1,598 (8) Table 3. Estimated ORs (95% CIs) by age groups for childhood cancers associated with residence at diagnosis in agriculturally intense counties in the U.S. NAACCR, 1995–2001, ICCC major sites and selected subgroups. Percent cropland Medium High Cancer type All cancers Leukemias Lymphoid leukemias Acute myeloid leukemias Lymphomas and reticuloendothelial Hodgkin lymphomas Non-Hodgkin lymphomas Central nervous system Astrocytomas Primitive neuroectodermal tumor Sympathetic nervous system tumors Neuroblastomas Retinoblastoma Renal tumors Wilms’ tumor Renal carcinoma Hepatic tumors Hepatoblastoma Malignant bone tumors Osteosarcoma Ewing’s sarcoma Soft-tissue sarcomas Rhabdomyosarcomas Germ cell, etc.a Carcinomas and other Thyroid carcinoma Malignant melanoma Other and unspeciﬁed aGerm cell, trophoblastic, and other gonadal neoplasms. No. 4,476 1,357 1,074 207 463 189 166 975 475 222 349 336 97 269 253 16 63 54 218 110 91 344 181 130 164 55 41 25 OR (95% CI) 1.0 (1.0–1.0) 1.0 (0.9–1.1) 1.0 (0.9–1.1) 1.2 (1.1–1.4) 1.1 (1.0–1.2) 1.3 (1.1–1.5) 1.1 (0.9–1.3) 1.1 (1.0–1.1) 1.1 (1.0–1.2) 1.2 (1.0–1.4) 1.2 (1.0–1.3) 1.2 (1.0–1.3) 1.2 (1.0–1.5) 1.3 (1.1–1.5) 1.3 (1.1–1.5) 2.3 (1.3–4.2) 1.6 (1.2–2.2) 1.7 (1.3–2.3) 1.2 (1.1–1.4) 1.3 (1.0–1.6) 1.8 (1.4–2.3) 1.3 (1.1–1.4) 1.5 (1.2–1.7) 1.3 (1.1–1.6) 1.1 (1.0–1.3) 1.8 (1.3–2.4) 1.6 (1.1–2.2) 2.9 (1.9–4.6)