Pesticide use and risk of Hodgkin lymphoma: results from the North American Pooled Project (NAPP).

PURPOSE: The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP). METHODS: Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2-4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient. RESULTS: In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04-6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02-33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00-3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28-7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34-4.97). CONCLUSION: In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.

Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project.

Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled × years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for ≤10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, ≤17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT.

The inclusion of women in studies of occupational cancer: a review of the epidemiologic literature from 1991-2009.

INTRODUCTION: Since the early 1990s, researchers have been concerned with the low rate at which women are included in epidemiologic studies of occupational cancer. A previous evaluation determined that one-third of articles published between 1970 and 1990 included women. METHODS: To assess whether there has been an improvement in recent years, papers on occupational cancer between 1991 and 2009 were reviewed in fifteen journals. RESULTS: The proportion of articles that included men remained stable around 90%, while the proportion of articles that included women increased substantially, from 39% in 1991-1995 to 62% in 2006-2009. Articles that assessed risk among men only or men and women presented a higher number of risk estimates and were more likely to evaluate dose-response relationships than studies including women. CONCLUSIONS: Despite advances in the inclusion of women in studies of occupational cancer, disparities remain in the number of studies of occupational cancer and depth of analysis in studies that included women.

Racial/ethnic differences in breast cancer survival by inflammatory status and hormonal receptor status: an analysis of the Surveillance, Epidemiology, and End Results data.

BACKGROUND: Compared to non-inflammatory breast cancer (non-IBC), inflammatory breast cancer (IBC) has less favorable survival and is more likely to be estrogen receptor (ER) and progesterone receptor (PR) negative. ER-/PR- tumors, regardless of histology, have less favorable survival. While black women are more likely to have IBC and ER-/PR- tumors than white women, it is unclear whether the racial disparity in survival is explained by these factors. The objective of this study was to assess racial/ethnic differences in breast cancer survival by inflammatory status and hormone receptor status. METHODS: This study examined breast cancer mortality among non-Hispanic white (NHW), Hispanic white, black, and Asian/Pacific Islander (API) women diagnosed between 1990 and 2004 using the National Cancer Institute's Surveillance, Epidemiology, and End Results data. Kaplan-Meier survival curves and Cox proportional hazard ratios (HRs) assessed the relationship between race/ethnicity and survival. RESULTS: Black women had significantly poorer survival than NHW women regardless of inflammatory status and hormone receptor status. Compared to NHWs, the HRs for black women were 1.32 (95 % confidence interval (CI) 1.21-1.44), 1.43 (95 % CI 1.20-1.69), and 1.30 (95 % CI 1.16-1.47) for IBC, IBC with ER+/PR+, and with ER-/PR-, respectively. Similar HRs were found for non-IBC, non-IBC with ER+/PR-, and non-IBC with ER-/PR-. API women had significantly better survival than NHW women regardless of inflammatory status and hormone receptor status. CONCLUSION: Compared to NHW women, black women had poorer survival regardless of inflammatory status and hormone receptor status and API women had better survival. These results suggest that factors other than inflammatory status and hormone receptor status may play a role in racial/ethnic disparities in breast cancer survival.

Recent trends in published occupational cancer epidemiology research: results from a comprehensive review of the literature.

OBJECTIVE: To assess trends in occupational cancer epidemiology research through a literature review of occupational health and epidemiology journals. METHODS: Fifteen journals were reviewed from 1991 to 2009, and characteristics of articles that assessed the risk of cancer associated with an occupation, industry, or occupational exposure, were incorporated into a database. RESULTS: The number of occupational cancer epidemiology articles published annually declined in recent years (2003 onwards) in the journals reviewed. The number of articles presenting dose-response analyses increased over the review period, from 29% in the first 4 years of review to 49% in the last 4 years. CONCLUSION: There has been a decrease in the number of occupational cancer epidemiology articles published annually during the review period. The results of these articles help determine the carcinogenicity of workplace exposures and permissible exposure limits, both of which may be hindered with a decline in research.

Hair dye use and risk of bladder cancer in the New England bladder cancer study.

Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies.

Genetic variation in metabolic genes, occupational solvent exposure, and risk of non-hodgkin lymphoma.

Using 1996-2000 data among Connecticut women, the authors evaluated whether genetic variation in 4 metabolic genes modifies organic solvent associations with non-Hodgkin lymphoma and 5 major histologic subtypes. P(interaction) values were determined from cross-product terms between dichotomous (ever/never) solvent variables and genotypes at examined loci in unconditional logistic regression models. The false discovery rate method was used to account for multiple comparisons. Overall associations between the chlorinated solvents dichloromethane (odds ratio (OR) = 1.69, 95% confidence interval (CI): 1.06, 2.69), carbon tetrachloride (OR = 2.33, 95% CI: 1.23, 4.40), and methyl chloride (OR = 1.44, 95% CI: 0.94, 2.20) and total non-Hodgkin lymphoma were increased among women TT for rs2070673 in the cytochrome P4502E1 gene, CYP2E1 (dichloromethane: OR = 4.42, 95% CI: 2.03, 9.62; P(interaction) < 0.01; carbon tetrachloride: OR = 5.08, 95% CI: 1.82, 14.15; P(interaction) = 0.04; and methyl chloride: OR = 2.37, 95% CI: 1.24, 4.51; P(interaction) = 0.03). In contrast, no effects of these solvents were observed among TA/AA women. Similar patterns were observed for diffuse large B-cell lymphoma and follicular lymphoma, as well as marginal zone lymphoma for dichloromethane. The weak, nonsignificant overall association between benzene and diffuse large B-cell lymphoma (OR = 1.29, 95% CI: 0.84, 1.98) was increased among women AA for rs2234922 in the microsomal epoxide hydrolase gene, EPHX1 (OR = 1.77, 95% CI: 1.06, 2.97; P(interaction) = 0.06). In contrast, no effect was observed among AG/GG women. Additional studies with larger sample size are needed to replicate these findings.

Impact of pesticide exposure misclassification on estimates of relative risks in the Agricultural Health Study.

BACKGROUND: The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES). METHODS: We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and a chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications. RESULTS: Correlations between urinary levels of 2,4-D and a chlorpyrifos metabolite and algorithm estimated intensity scores were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4) and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with kilograms of active ingredient used, duration of application, or number of acres treated were lower and ranged from -0.36 to 0.19. These findings indicate that a priori expert-derived algorithm scores were more closely related to measured urinary levels than individual exposure determinants evaluated here. Estimates of potential bias in relative risks based on the correlations from the AHS/PES indicate that non-differential misclassification of exposure using the algorithm would bias estimates towards the null, but less than that from individual exposure determinants. CONCLUSIONS: Although correlations between algorithm scores and urinary levels were quite good (ie, correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.

Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.

In light of the relationship between immune system dysregulation and multiple myeloma (MM) risk, we investigated whether genetic variation in 92 immune function genes among 77 gene regions are associated with MM susceptibility in a population-based case-control study (108 cases and 482 controls) conducted among Caucasian women in Connecticut. Tagging single-nucleotide polymorphisms (SNPs; N = 870) were selected using a pairwise linkage-disequilibrium based algorithm. Odds ratios (ORs) and 95% confidence intervals (CIs) for SNP genotypes were estimated using unconditional logistic regression. Tests of association for gene regions were conducted using the minP test. We applied the false discovery rate (FDR) method to the minP test results as a means of controlling for multiple comparisons. The CD4 gene region located on 12p13-q13 (minP = 0.0009), had an FDR value <0.1. In this region, a total of six tag SNPs in two genes (CD4 and LAG3) were significantly associated with MM risk (P(trend)<0.05), with the strongest association observed for the CD4 variant rs11064392 (OR(AG/GG) = 2.53, 95% CI = 1.59-4.02). Our findings suggest that genetic variation in CD4 may influence susceptibility to MM. Additional studies are needed to replicate these findings and, more generally, to explore the manner in which genes and receptors may influence the pathogenesis of this poorly understood malignancy.

Occupational exposure to solvents and risk of non-Hodgkin lymphoma in Connecticut women.

A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996-2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), average probability (P < 0.01), cumulative intensity (P = 0.01), and cumulative probability (P < 0.01) level of organic solvent and with average probability level (P = 0.02) and cumulative intensity level of chlorinated solvent (P = 0.02). Analyses by NHL subtype showed a risk pattern for diffuse large B-cell lymphoma similar to that for overall NHL, with stronger evidence of an association with benzene exposure. Results suggest an increased risk of NHL associated with occupational exposure to organic solvents for women.

Genetic variations in xenobiotic metabolic pathway genes, personal hair dye use, and risk of non-Hodgkin lymphoma.

From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T>A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A>G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies.

Glyphosate use and associations with non-Hodgkin lymphoma major histological sub-types: findings from the North American Pooled Project.

Objectives Some epidemiological studies have suggested positive associations between glyphosate use and non-Hodgkin lymphoma (NHL), but evidence is inconsistent and few studies could evaluate histological sub-types. Here, associations between glyphosate use and NHL incidence overall and by histological sub-type were evaluated in a pooled analysis of case-control studies. Methods The analysis included 1690 NHL cases [647 diffuse large B-cell lymphoma (DLBCL), 468 follicular lymphoma (FL), 171 small lymphocytic lymphoma (SLL), and 404 other sub-types] and 5131 controls. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for NHL overall and sub-types with self-reported ever/never, duration, frequency, and lifetime-days of glyphosate use. Results Subjects who ever used glyphosate had an excess of NHL overall (OR 1.43, 95% CI 1.11-1.83). After adjustment for other pesticides, the OR for NHL overall with "ever use" was 1.13 (95% CI 0.84-1.51), with a statistically significant association for handling glyphosate >2 days/year (OR 1.73, 95% CI 1.02-2.94, P-trend=0.2). In pesticide-adjusted sub-type analyses, the ordinal measure of lifetime-days was statistically significant (P=0.03) for SLL, and associations were elevated, but not statistically significant, for ever years or days/year of use. Handling glyphosate >2 days/year had an excess of DLBCL (OR 2.14, 95% CI 1.07-4.28; P-trend=0.2). However, as with the other sub-types, consistent patterns of association across different metrics were not observed. Conclusions There was some limited evidence of an association between glyphosate use and NHL in this pooled analysis. Suggestive associations, especially for SLL, deserve additional attention.

Non-Hodgkin lymphoma risk and organophosphate and carbamate insecticide use in the north American pooled project.

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14-1.81) compared with never users. Categories using tertiles of duration (<4 yrs., 4-12 yrs., and >12 yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR<4vsUnex = 1.33 (0.88, 2.03), OR4-12vsUnex = 1.42 (1.02, 1.96), OR>12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11-2.27) and DLBCL (OR = 1.61; 95% CI: 1.16-2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes.

The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma.

Characteristic chromosomal abnormalities are associated with specific histological subtypes of non-Hodgkin lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL, occurring in 70%-90% of cases of follicular lymphoma, 20%-30% of diffuse large B-cell lymphoma, and 5%-10% of other less common subtypes. The t(14;18)-positive NHL may represent a homogenous group and, consequently, increase etiologic specificity in epidemiological studies. Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two population-based, case-control studies addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Both studies found that the association between pesticide exposures and risk of NHL was largely limited to t(14;18)-positive NHL cases. However, the findings regarding cigarette smoking, family history of hematopoietic cancer, and hair dye use were not entirely consistent. These results indicate that defining subgroups of NHL according to t(14;18) status may be useful for etiologic research, particularly for exposures that are genotoxic or may contribute to the development of NHL through pathways involving the t(14;18). Studies to further evaluate these associations and delineate the effects of various exposures in other genetically defined subgroups of NHL are warranted.

Personal use of hair dye and the risk of certain subtypes of non-Hodgkin lymphoma.

Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.

Dietary factors and risk of t(14;18)-defined subgroups of non-Hodgkin lymphoma.

OBJECTIVE: To evaluate the associations between diet and non-Hodgkin lymphoma (NHL) according to t(14;18) status, one of the most common chromosomal abnormalities in NHL, as t(14;18)-positive NHL represents a genetically more homogeneous group than NHL overall. METHODS: We determined the presence of the t(14;18)(q32;q21) by fluorescence in situ hybridization in 172 of 175 tumor blocks from a population-based, case-control study conducted in Nebraska during 1983-1986. Information on the frequency of consumption as an adult of 30 food items was derived from the parent case-control study. Dietary factors in 60 t(14;18)-positive and 87 t(14;18)-negative cases were compared with 1,075 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using polytomous logistic regression. RESULTS: The risk of t(14;18)-positive NHL for the highest versus the lowest approximate tertile of intake was elevated for milk (OR = 2.2; 1.0-5.0) and dietary nitrite (OR = 2.8; 1.3-6.1), whereas coffee consumption was inversely associated with risk (OR = 0.4; 0.2-0.7). We also found inverse associations between the intake of fish (OR = 0.5; 0.3-1.0) and carotene (OR = 0.5; 0.2-0.9) and risk of t(14;18)-negative NHL. There was no association between the intake of meats, vegetables, protein, or vitamin C and risk of either t(14;18)-positive or t(14;18)-negative NHL. CONCLUSION: We observed differences in associations between diet and t(14;18)-defined subgroups of NHL. These findings should be interpreted cautiously because of the small sample.

Lead, genetic susceptibility, and risk of adult brain tumors.

BACKGROUND: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. METHODS: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. RESULTS: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. CONCLUSIONS: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype.

Residential herbicide use and risk of non-Hodgkin lymphoma.

CONTEXT: Environmental exposure to herbicides has been hypothesized to contribute to the long-term increase in non-Hodgkin lymphoma (NHL). OBJECTIVE: To estimate the effects of residential herbicide exposure on NHL risk. DESIGN: Population-based case-control study. SETTING: Iowa and metropolitan Detroit, Los Angeles, and Seattle, 1998 to 2000. PARTICIPANTS: NHL patients ages 20 to 74 years and unaffected residents identified by random digit dialing and Medicare eligibility files. MAIN OUTCOME MEASURES: Computer-assisted personal interviews (1,321 cases, 1,057 controls) elicited data on herbicide use at each home occupied since 1970. Levels of 2,4-dichlorophenoxy-acetic acid and dicamba were measured in dust taken from used vacuum cleaner bags in the current home (679 cases, 510 controls who had owned at least half of their carpets for > or = 5 years). RESULTS: Herbicide use on the lawn or garden was similar among cases and controls (adjusted relative risk, 1.02; 95% confidence interval, 0.84-1.23). Estimated risk did not increase with greater duration, frequency, or total number of applications of herbicides to the lawn, the garden, or to both combined. Risk was not elevated for respondents who applied the herbicides themselves and not for those exposed during the 1970s, 1980s, or 1990s. We detected 2,4-dichlorophenoxy-acetic acid equally often in homes of cases and controls (78%). We found dicamba in homes of 15% of cases and 20% of controls. We also found no elevation in risk among the respondents who had the highest dust levels and highest self-reported exposures. We found no consistent patterns for specific histologies. CONCLUSIONS: We found no detectable excess associated with residential exposures. Residential herbicide exposures are unlikely to explain the long-term increase in NHL.

Mortality among participants in the agricultural health study.

PURPOSE: This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses. METHODS: This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 21-page enrollment questionnaire. Mortality assessment from enrollment (1994-1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths. RESULTS: Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies. CONCLUSIONS: Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity.

Agricultural pesticide use, familial cancer, and risk of non-Hodgkin lymphoma.

To investigate whether the association between agricultural pesticide use and the risk of non-Hodgkin's lymphoma (NHL) is modified by a family history of hematopoietic cancer, including leukemia, myeloma, and lymphoma, we analyzed pooled data on white men from three population-based, case-control studies of NHL conducted in Iowa/Minnesota, Kansas, and Nebraska. Information on the agricultural use of insecticides, fungicides, and herbicides; a family history of cancer; and other risk factors was obtained by interviewing 973 cases and 2,853 controls or, if deceased, their next-of-kin (37% of cases, 43% of controls). The NHL risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, state of residence, type of respondent, and use of hair dye. Compared to men with no family history of cancer, the ORs (95% CIs) of NHL was 1.5 (1.3-1.8) for men with a family history of nonhematopoietic cancer, and 2.7 (1.9-3.7) for those with a history of hematopoietic cancer among first-degree relatives. This positive association was noted for each group of NHL defined according to the Working Formulation, and was most pronounced for small lymphocytic NHL. Among direct respondents, farmers who used pesticides and had a positive family history of cancer or hematopoietic cancer were not at elevated risk of NHL, compared to nonfarmers who had no family cancer history. However, among proxy respondents, ORs were elevated for farmers who had a positive family history of hematopoietic cancer and used animal insecticides (OR = 4.6; 1.9-11.2), crop insecticides (OR = 4.7; 1.6-13.4), or herbicides (OR = 4.9; 1.7-14.2), although the interaction of family history of cancer and agricultural pesticide use was not statistically significant. In summary, the joint effects of the family cancer history and pesticide use were limited to proxy respondents with wide CIs and, thus, provide little evidence that a family history of cancer modifies the association of agricultural exposures with NHL.