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Insecticide use has been linked to increased risk of non-Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self-reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype-specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20-2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17-2.16: FL, SLL) and DDT (OR = 1.36, 1.06-1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (P trend = 1.7 × 10 -4 ), chlordane (P trend = 1.0 × 10 -3 ) and DDT (P trend = 4.2 × 10 -3 ), however, the exposure-response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45-9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75-16.53; P trend = 3.6 × 10 -3 ). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

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.

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), OR 4-12vsUnex  = 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., (Published by Elsevier Ltd.)

Background: Nitrate is a widespread contaminant of drinking water, but its potential health effects are unclear. In the body, nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds, known animal carcinogens. N-nitroso compound formation is inhibited by certain nutrients, such as vitamin C, and increased by meat intake., Methods: We investigated the association of nitrate in public water supplies with incident colon and rectum cancers in a case-control study conducted in Iowa from 1986 to 1989. Nitrate levels in Iowa towns were linked to the participants' water source histories. We focused our analyses on the period from 1960 onward, during which nitrate measurements were more frequent, and we restricted analyses to those persons with public water supplies that had nitrate data (actual or imputed) for greater than 70% of this time period (376 colon cancer cases, 338 rectum cancer cases, and 1244 controls)., Results: There were negligible overall associations of colon or rectum cancers with measures of nitrate in public water supplies, including average nitrate and the number of years with elevated average nitrate levels. For more than 10 years with average nitrate greater than 5 mg/L, the odds ratio (OR) for colon cancer was 1.2 (95% confidence interval [CI] = 0.9-1.6) and for rectum the OR was 1.1 (CI = 0.7-1.5). However, nitrate exposure (>10 years with average nitrate >5 mg/L) was associated with increased colon cancer risk among subgroups with low vitamin C intake (OR = 2.0; CI = 1.2-3.3) and high meat intake (OR = 2.2; CI = 1.4-3.6). These patterns were not observed for rectum cancer., Conclusions: Our analyses suggest that any increased risk of colon cancer associated with nitrate in public water supplies might occur only among susceptible subpopulations.

Background: Vital status followup for a retrospective cohort mortality study of 9,961 male aerial pesticide applicators was extended beyond a previous study (1965-1979) (Cantor et al. 1991), through December 31, 1988., Methods: Rate ratios (RR) were used to compare directly adjusted mortality rates between applicators and a comparison cohort of 9,969 flight instructors. Standardized mortality ratios (SMR) were calculated for comparisons with the U.S. white male population., Results: Among applicator pilots, there were 1,441 deaths, and among instructors, 1,045. In both groups, aircraft accidents were the major cause of death (446 applicators; 234 instructors). Compared with flight instructors, aerial applicator pilots were at significantly elevated risk for all causes of death (risk ratio = 1.34) and for malignant neoplasms (1.18), non-motor vehicle accidents (1.71), motor vehicle accidents (1.69), and stroke (1.91). Pancreatic cancer (2.71) and leukemia (3.35) were significantly elevated. Applicators were at lower risk of colon cancer (0.51) and multiple myeloma (0.23) mortality. Based on U.S. rates, the SMR for all causes of death among applicators was 111 (95% confidence interval (CI) = 105-117) and among instructors, 81 (CI = 76-85)., Conclusions: Aircraft accidents were a major cause of mortality in both applicator and flight instructor cohorts. Several other causes of death, some possibly related to pesticide exposure, were also elevated among pesticide applicator pilots. Published 1999 Wiley-Liss, Inc.

Purpose: The purpose of this study was to evaluate the role of physical activity in the development of non-Hodgkin's lymphoma (NHL)., Methods: Incident NHL cases and population-based controls were identified from three case-control studies conducted in four midwestern states: Iowa, Kansas, Minnesota, and Nebraska. A total of 1177 cases (993 men, 184 women) and 3625 controls (2918 men, 707 women) were interviewed. Usual occupation (all states) and lifetime occupational histories (Iowa and Minnesota only), obtained from interviews, were classified for energy expenditure (EE) and sitting time. Odds ratios (OR) and 95% confidence intervals were calculated comparing moderate and high activity levels with sedentary levels., Results: There was no evidence of an association between NHL and occupational physical activity measured either by EE or sitting time. Among men, the OR associated with usual occupation moderate and high EE were 1.1 and 1.0, respectively. For sitting time, the OR were also 1.1 and 1.0 for moderate and high activity, respectively. Among women, slight nonsignificant elevations in risk of NHL were observed among the high energy level and high activity sitting categories. The trends were not significant. There was no evidence of confounding or effect modification by vital status, hair dye use, or solvent exposure. Among subjects with lifetime occupational histories, there were no significant increases or trends for cumulative or average EE or sitting time. There was no association between occupational physical activity and NHL., Conclusion: Research on nonoccupational physical activity, which in the U.S. is likely the more important component of daily activity than occupational activity, may still be warranted given the laboratory evidence linking physical activity and immune function, an important factor in the etiology of NHL.

The role of tobacco in the etiology of non-Hodgkin's lymphoma (NHL) was evaluated in a combined analysis of data from three population-based case-control studies conducted in four midwestern states of the United States: Nebraska, Iowa, Minnesota, and Kansas. Interviews were obtained from 1,177 cases (993 men, 184 women) and 3,625 controls (2,918 men, 707 women) or, if deceased, from their next-of-kin. Overall, there was no association between NHL and tobacco use (odds ratio [OR] = 1.0, 95 percent confidence interval [CI] = 0.8-1.1) or cigarette smoking (OR = 1.0, CI = 0.8-1.1). A slight negative association evident in analyses by intensity and duration of smoking was not present when interviews from proxy respondents were eliminated. There was a suggestion of a positive association between smoking and NHL among women (OR = 1.3, CI = 0.9-1.9), although there was no clear exposure-response relationship. This large case-control analysis provides no evidence that smoking is linked to the development of NHL among men. The possible role of smoking in the etiology of NHL among women needs further evaluation.

Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background.

Mortality records from 24 states, gathered from 1984 to 1989 and coded for occupation and industry, were used to develop leads to workplace exposures as possible breast cancer risk factors. A case-control approach was used, with separate analyses for blacks and whites. After excluding homemakers, 33,509 cases and 117,794 controls remained. A job exposure matrix was used to estimate the probability and level of 31 workplace exposures. After adjusting for socioeconomic status, suggestive associations for probability and level of exposure were found for styrene, several organic solvents (methylene chloride, carbon tetrachloride, formaldehyde), and several metals/metal oxides and acid mists. Because of the methodologic limitations of this study, its primary value is in suggesting hypotheses for further evaluation. The findings for styrene, selected solvents, and metals and metal-related exposures deserve additional study.

Background: Despite theoretically higher requirements for water due to physiologic demands of pregnancy and lactation, little is known of actual ranges of intake in pregnant and lactating women., Methods: Population-based estimates of total water and tapwater intake in women of reproductive age were derived using data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non-pregnant, non-lactating control women., Results: Total water intake (mean +/- SD) was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310 +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to or greater than 3,000 g/day among 7 percent of control women, 11 percent of pregnant women, and 13 percent of lactating women. Tapwater intake was equal to or greater than 2,000 g/day among 10 percent of control women, 15 percent of pregnant women, and 8 percent of lactating women., Conclusions: These results should be useful in estimating amounts of nutrients and toxic substances that women of reproductive age obtain through the water supply.

A cohort mortality study was conducted of male aerial pesticide applicators and flight instructors identified from computerized Federal Aviation Administration medical examination records from 1965-1979. Vital status of 9,677 applicators and 9,727 instructors was determined through January 1, 1980, and standardized mortality ratios (SMRs) were calculated. The overall SMR was 127 for applicators (699 deaths) and 93 for instructors (454 deaths). Fatalities from nonmotor vehicle accidents, mostly aircraft crashes, were in notable excess (SMR = 1,168 among applicators, 630 among instructors), whereas deaths from most chronic diseases, including all cancer, was below expectation (e.g., for arteriosclerotic heart disease, SMR = 52 among applicators and 50 among instructors). The ability of the study to assess cancer risk among applicators was limited by a relatively brief follow-up period. However, 8 applicators (SMR = 171), but only 1 flight instructor (SMR = 24), died of leukemia, and small, nonsignificant risk elevations for some other cancer sites among applicators were observed and warrant continued follow-up.

Data from a continuing multiyear seroprevalence survey of human T-lymphotropic virus types I or II (HTLV-I/II) among intravenous drug users in seven U.S. locations were analyzed to detect demographic patterns of seropositivity and coinfection with human immunodeficiency virus type 1 (HIV-1). Seropositivity for HTLV-I/II and HIV-1 was detected by whole-virus enzyme immunoassay, with Western blot confirmation. Of 1,800 subjects recruited from methadone maintenance and detoxification clinics, 207 (11.5%) were infected with HTLV-I/II. Seropositivity for HTLV-I/II varied by racial group, age, sex, and geographic location. Blacks had a higher (age- and location-adjusted) infection rate (17.1%) than Hispanics (8.7%) or whites (5.6%), and seropositivity showed a strong gradient with increasing age. Females had a slightly higher rate (14.0%) than males (10.0%), after adjustment for age and location. Among the seven locations, the rate varied from approximately 1% (Miami and Baltimore) to 20% (Los Angeles), although the former rates were based on relatively few subjects (47 and 65, respectively). Overall, the occurrence of coinfection by HIV-1 and HTLV-I/II did not occur more frequently than expected by chance.

The potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies. This ecological study investigated the association between U.S. county forage selenium status and site- and sex-specific county cancer mortality rates (1950-1969) using weighted least squares regression. Consistent, significant (p less than .01) inverse associations were observed for cancers of the lung, rectum, bladder, esophagus, and cervix in a model limited to rural counties and for cancers of the lung, breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties. No consistent significant positive associations were observed in the rural county models. This remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality.

Concern has recently been voiced over possible chronic toxicity associated with chlorination of public drinking water supplies in the United States. This paper reviews the available evidence and the studies underway to further evaluate hypothesized associations between cancer risk and byproducts of chlorination. Preliminary data from measures of halogenated volatiles and personal exposure histories from respondents in a large epidemiologic study of bladder cancer are presented. These data support the use in epidemiologic studies of categorical measures of exposure and suggest that results from completed case-control studies, based on death certificates, may have underestimated the true risk of exposure to chlorination by-products. The current generation of studies which use a case-control interview design offer many advantages over earlier efforts to evaluate this issue.

Associations between site- and sex-specific county cancer mortality rates and levels of trihalomethanes (THM's) in drinking water were examined after adjustment of rates for the influence of multiple socioeconomic, industrial, and demographic factors. U.S. counties with sampled supplies were grouped by percent of the county population receiving water from the supply, as well as by region of the country. For two sites (bladder and lung), county rates were also adjusted for the activity level in specific high-risk industries. Positive correlations with THM levels were observed for several cancers, including bladder and brain cancers in both sexes, and non-Hodgkin's lymphoma and kidney cancer in males. Stomach cancer in females showed a negative association. Bladder cancer mortality rates showed the strongest and most consistent association with a THM exposure index, after control for differences in social class, ethnic group, urban versus rural residence, region of the United States, and industrialization of the county. These ecologic associations suggested that further evaluation in analytic investigations is warranted.

Data from a population-based case-control interview study of incident bladder cancer in 10 areas of the United States were used to estimate relative risks among white men (2,116 cases, 3,892 controls) and women (689 cases, 1,366 controls) according to beverage intake level and type of water source. Individual year-by-year profiles of water source and treatment were developed by linking lifetime residential information with historical water utility data from an ancillary survey. Risk of bladder cancer increased with intake level of beverages made with tap water. The odds ratio (OR) for the highest vs. lowest quintile of tap water consumption was 1.43 [95% confidence interval (CI) = 1.23, 1.67; chi 2 for trend = 26.3, P less than .001]. The risk gradient with intake was restricted to persons with at least a 40-year exposure to chlorinated surface water and was not found among long-term users of nonchlorinated ground water. The ORs for the highest vs. lowest quintiles of tap water intake were 1.7 and 2.0, respectively, among subjects with 40-59 and greater than or equal to 60 years' exposure. Duration of exposure to chlorinated surface water was associated with bladder cancer risk among women and nonsmokers of both sexes. Among non-smoking respondents with tap water consumption above the population median, the OR increased with exposure duration to a level of 3.1 (CI = 1.3, 7.3; chi 2 for trend = 6.3, P = .01) for greater than or equal to 60 years of residence at places served by chlorinated surface water (vs. non-chlorinated ground water users). These results extend findings of earlier epidemiologic studies and are consistent with environmental chemistry and toxicologic data demonstrating the presence of genotoxic by-products of chlorine disinfection in treated surface waters.

Age-adjusted mortality rates for non-Hodgkin's lymphoma in counties of the contiguous United States were examined by sex and race during 1950 to 1975 and were correlated through 1969 with demographic and industrial data. Mortality was consistently elevated in counties with large populations, especially in those with higher income and education levels. Among males, but not females, elevated rates appeared in counties with high percentages of residents of Russian or Greek descent. A series of contiguous counties with high rates was seen along the coast of California. Lower rates in the South were explained in a multivariate analysis by the generally lower socioeconomic levels in this region. Counties with industrial concentration in food packing showed higher mortality rates among males than did comparable counties without these industries. All regions and all sex-race groups showed an increase over time in mortality from non-Hodgkin's lymphoma, especially reticulum cell sarcoma.