Pancreatic cancer and serum organochlorine levels.

Occupational exposure to p,p'-dichlorodiphenyltrichloroethane (DDT) has been associated with increased pancreatic cancer risk. We measured organochlorine levels in serum obtained at the study enrollment from 108 pancreatic cancer cases and 82 control subjects aged 32-85 years in the San Francisco Bay Area between 1996 and 1998. Cases were identified using rapid case-ascertainment methods; controls were frequency-matched to cases on age and sex via random digit dial and random sampling of Health Care Financing Administration lists. Serum organochlorine levels were adjusted for lipid content to account for variation in the lipid concentration in serum between subjects. Median concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE, 1290 versus 1030 ng/g lipid; P = 0.05), polychlorinated biphenyls (PCBs; 330 versus 220 ng/g lipid; P<0.001), and transnonachlor (54 versus 28 ng/g lipid; P = 0.03) were significantly greater among cases than controls. A significant dose-response relationship was observed for total PCBs (P for trend <0.001). Subjects in the highest tertile of PCBs (> or =360 ng/g lipid) had an odds ratio (OR) of 4.2 [95% confidence interval (CI) = 1.8-9.4] compared to the lowest tertile. The OR of 2.1 for the highest level of p,p'-DDE (95% CI = 0.9-4.7) diminished (OR = 1.1; 95% CI = 0.4-2.8) when PCBs were included in the model. Because pancreatic cancer is characterized by cachexia, the impact of this on the serum organochlorine levels in cases is difficult to predict. One plausible effect of cachexia is bioconcentration of organochlorines in the diminished lipid pool, which would lead to a bias away from the null. To explore this, a sensitivity analysis was performed assuming a 10-40% bioconcentration of organochlorines in case samples. The OR associated with PCBs remained elevated under conditions of up to 25% bioconcentration.

K-ras and p53 in pancreatic cancer: association with medical history, histopathology, and environmental exposures in a population-based study.

Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.

Reproductive toxins and alligator abnormalities at Lake Apopka, Florida.

The alligator population at Lake Apopka in central Florida declined dramatically between 1980 and 1987. Endocrine-disrupting chemicals and specifically DDT metabolites have been implicated in the alligators' reproductive failure. The DDT metabolite hypothesis is based largely on the observation of elevated concentrations of p,p-DDE and p,p-DDD in alligator eggs obtained from Lake Apopka in 1984 and 1985. In the following commentary, we draw attention to two nematocides that are established reproductive toxins in humans, dibromochloropropane (DBCP) and ethylene dibromide (EDB), which could also have played a role in the reproductive failure observed in alligators from Lake Apopka in the early 1980s.

Determinants of polybrominated biphenyl serum decay among women in the Michigan PBB cohort.

Accidental contamination of the food chain in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. Serum was collected and analyzed for PBB at the time of enrollment and for targeted studies in the following years. We used the archived PBB data to study the elimination of PBB and to identify factors associated with elimination. A total of 380 women >= 16 years of age who had an initial PBB level of 2 ppb and at least two serum samples drawn when they were not pregnant were included in the analysis. The mean initial PBB level was 20.9 ppb (median 4) and mean time between the first and last measurement was 4.2 years (range 0.5-11.1). PBB was assumed to reach equilibrium in the body before substantial amounts were eliminated and before the first serum measurements were taken; therefore, the entire body was modeled as a single compartment for PBB with exponential decay. Subject-specific decay rate estimates were regressed on predictor variables including initial age, body mass index (BMI), smoking history, breast-feeding duration, and parity. In women with an initial PBB level < 10 ppb, the median half-life was 12.9 years; in those with > 10 ppb, the median half-life was 28.7 years. Decay was significantly slower among women with an initial BMI at or above the median (BMI >= 23). The calculated half-life values are estimates of decay and can be used to estimate body burden of PBB at various points in time other than at the time of serum collection.

Breast-feeding among women exposed to polybrominated biphenyls in Michigan.

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Patterns of genetic alterations in pancreatic cancer: a pooled analysis.

Both K-ras and p53 gene mutations are found commonly in pancreatic tumors. Analysis of the mutational patterns may provide insight into disease etiology. To further describe the mutational patterns of pancreatic cancer and to assess the evidence to date, we performed a pooled analysis of the published data on genetic mutations associated with pancreatic ductal adenocarcinoma. We included data from studies that evaluated point mutations in the two genes most studied in pancreatic cancer, K-ras and p53. A majority of the 204 tumors had mutations in at least one gene, with 29% having both K-ras and p53 mutations, 39% with K-ras mutation alone, and 16% having p53 mutation alone. Sixteen percent of tumors lacked mutation in either gene. K-ras mutations were present in high frequencies in all tumor grades (>69%). A statistically significant trend was observed for p53 mutation with higher tumor grade (P = 0.04). For K-ras, G2 and G3 grades, combined, had notably higher prevalences of mutation than G1 (P = 0.004). CGT mutations in K-ras codon 12 were marginally associated with lower tumor grade (P for trend = 0.09), and these tumors were somewhat less likely to have a p53 mutation than tumors with other K-ras mutations (P = 0.06). In the 59 K-ras+/p53+ tumors, 64% had the same type of mutation (transition or transversion) in both genes, suggesting a common mechanism. The mutational pattern of p53 in pancreatic cancer is similar to bladder cancer, another smoking-related cancer, but not to lung cancer. Analyses of molecular data, such as that performed here, present new avenues for epidemiologists in the study of the etiology of specific cancers.

Micronuclei and other nuclear anomalies in buccal smears: methods development.

Laboratory work aimed at improving the epidemiologic utility of an innovative genotoxicity assay is described. The exfoliated cell micronucleus assay involves microscopic analysis of epithelial smears to determine the prevalence of micronucleation, an indicator of structural or numerical chromosome aberrations. While the assay holds promise for the study of epithelial carcinogens, it is hampered by the fact that exfoliated cells are moribund and undergo degenerative phenomena that can produce extranuclear objects difficult to distinguish from classical micronuclei. Modifications in the protocol were assessed in sample buccal smears from several study populations: radiotherapy patients, nonusers of tobacco, and snuff users. Refinements in micronucleus scoring criteria and the inclusion of other nuclear anomalies in the scoring system are proposed. We demonstrate that our criteria are successful in detecting excess micronucleation in positive controls. We also provide evidence that other nuclear anomalies are at least as common as micronucleation and that therefore there is the potential for extensive misclassification. Reliability was assessed in duplicate readings.

Interim results of the study of particulates and health in Atlanta (SOPHIA).

Substantial evidence supports an association of particulate matter (PM) with cardiorespiratory illnesses, but little is known regarding characteristics of PM that might contribute to this association and the mechanisms of action. The Atlanta superstation sponsored by the Electric Power Research Institute as part of the Aerosol Research and Inhalation Epidemiology Study (ARIES) study is monitoring chemical composition of ambient particles by size fraction, as well as a comprehensive suite of other pollutants, at a site in downtown Atlanta during the 25-month period, August 1, 1998-August 31, 2000. Our investigative team is making use of this unique resource in several morbidity studies, called the "Study of Particulates and Health in Atlanta (SOPHIA)". The study includes the following components: (1) a time series investigation of emergency department (ED) visits for the period during which the superstation is operating; (2) a time series investigation of ED visits during the 5 years prior to implementation of the superstation; and (3) a study of arrhythmic events in patients equipped with automatic implantable cardioverter defibrillators (AICDs) for the period January 1, 1993-August 31, 2000. Thirty-three of 39 Atlanta area EDs are participating in the ED studies, comprising over a million annual ED visits. In this paper, we present initial analyses of data from 18 of the 33 participating EDs. The preliminary data set includes 1,662,713 ED visits during the pre-superstation time period and 559,480 visits during the superstation time period. Visits for four case groupings--asthma, chronic obstructive pulmonary disease (COPD), dysrhythmia, and all cardiovascular diseases (CVDs) combined--have been assessed relative to daily air quality indices, controlling for long-term temporal trends and meteorologic variables, using general linear models, generalized estimating equations and generalized additive models. Single-pollutant models predicting case visitation rates using moving averages of 0-, 1-, and 2-day lagged air quality variables were run. For the pre-superstation period, PM10 (24-h), ozone (8-h), SO2 (1-h), NO2 (1-h) and CO (1-h) were studied. For the first 12 months of superstation operation, the following air quality variables of a priori interest were available: ozone (8-h), NO2 (1-h), SO2 (1-h), CO (1-h), and 24-h measurements of PM10, coarse PM (PM 2.5-10 microm), PM2.5, polar VOCs, 10-100 nm particulate count and surface area, and in the PM2.5 fraction: sulfates, acidity, water-soluble metals, organic matter (OM), and elemental carbon (EC). During the pre-superstation time period, statistically significant, positive associations were observed for adult asthma with ozone, and for COPD with ozone, NO2 and PM10. During the superstation time period, the following statistically significant, positive associations were observed: dysrhythmia with CO, coarse PM, and PM2.5 EC; and all CVDs with CO, PM2.5 EC and PM2.5 OM. While covariation of many of the air quality indices limits the informativeness of this analysis, the study provides one of the first assessments of PM components in relation to ED visits.

Measurement of PCBs, DDE, and hexachlorobenzene in cord blood from infants born in towns adjacent to a PCB-contaminated waste site.

There are limited data on the concentrations of common contaminants--polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (pp'-DDE) and hexachlorobenzene (HCB)--in umbilical cord blood. Cord blood provides the primary direct measure of prenatal exposure to these contaminants, the key determinant of PCBs' neurodevelopmental toxicities. The objective of this study was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751 infants who were born between 1993 and 1998 to mothers residing adjacent to a PCB-contaminated harbor in New Bedford, Massachusetts, and for whom the neurodevelopmental toxicities of these compounds are being studied. We refined standard analytic methods to optimize the sensitivity and precision of trace-level PCB, p,p'-DDE, and HCB measurements in blood. Using these methods, we measured the concentrations of 51 individual PCBs, their sum (sum(PCB)), p,p'-DDE, and HCB in cord serum. With correction for background contamination, the respective mean+/-SD cord serum concentrations of sum(PCB), p,p'-DDE, and HCB were 0.54+/-0.83, 0.48+/-0.94, and 0.03+/-0.04 ng/g serum. These concentrations were generally lower than those in most of the few published studies with congener-specific measures of PCBs in cord blood. However, for less-chlorinated PCB congeners (e.g., congeners 99 and 118), study samples had concentrations comparable to those in other populations, including groups at risk for high dietary PCB exposure. Of note, the contaminated harbor sediment has a relatively high proportion of less-chlorinated PCB congeners. Thus, although the sum(PCB) in study infants was not higher than concentrations in infants studied elsewhere, the relative predominance of less-chlorinated congeners was generally consistent with the characteristics of the contaminated site.

Occupational chlorophenol exposure and non-Hodgkin's lymphoma.

Occupational exposure to chlorophenols is suspected to increase non-Hodgkin's lymphoma (NHL) risk. This association was examined using data on 995 NHL cases and 1783 controls from the Selected Cancers Study, a population-based case-control study of men aged 32 to 60 years from eight population-based cancer registries conducted from 1984 to 1988. Potential chlorophenol exposure was characterized by an industrial hygienist using intensity estimates and confidence ratings, based upon review of verbatim job histories. Cases with substantial chlorophenol exposure had a significantly greater number of years of chlorophenol exposure (median years: cases, 4.0; controls, 2.0; P = 0.046); however, in conditional logistic regression models, the odds ratio for more than 8 years of substantial exposure was 1.51 (95% CI, 0.88 to 2.59). Overall, the findings do not provide strong support for an association with NHL risk. Chlorophenol exposure in this study is not based upon measured values and, therefore, may fail to characterize actual chlorophenol exposures accurately. Because of the large presence of machinists in the potentially chlorophenol-exposed group, these results may be underestimated by exposure misclassification if these subjects were not exposed to chlorophenolic biocides. However, these results are consistent with other findings, which suggest that chlorophenol exposure is not likely to be a strong risk factor for NHL.

Agricultural exposure history among African-American farmers in Georgia.

Agricultural exposures differ across the United States by region, calendar time period, and agricultural practice, but most of the published literature focuses on white men in the Midwest. A pilot study was conducted to explore the breadth and diversity of farming practices over time among African-American farmers in Georgia whose exposures may differ in important ways. Using a comprehensive life events calendar questionnaire, 17 male African-American farmers aged 36 to 86 yr residing in southeastern Georgia were interviewed regarding their agricultural history in July 1997. Most men (15/17) reported working on multiple farms in their lifetime; 3 men worked on 5 different farms during their lifetime. These farmers reported using more chemicals during their lifetime than farmers in the Midwest. Used motor oil was the most frequently reported insecticide applied to animals; this apparently common practice has not been described in the literature and should be better understood since its use may result in dermal exposure to polyaromatic hydrocarbons. Better characterization of regionally specific farming history and individual farming practices will facilitate studies of the health effects of farming.

Mortality studies of machining-fluid exposure in the automobile industry. II. Risks associated with specific fluid types.

Excesses of digestive and respiratory cancers have been reported previously in association with exposure to machining fluids, agents in widespread use as coolants and lubricants in machining operations. Previous studies have had limited power to distinguish the effects of the different types of machining fluids in use. In a cohort of over 30,000 workers employed at two automotive plants in Michigan, mortality patterns were studied in relation to exposure to each of the three major fluid types--straight oils, soluble oils, and synthetic fluids. Standardized mortality ratios were estimated for subgroups of the cohort ever exposed to each of the three fluid types, and Poisson regression analyses were used to assess trends in risk with duration of exposure. The data suggest modest positive associations between exposure to straight oils and rectal, laryngeal, and prostatic cancer and a negative association between soluble and synthetic fluid exposure and lung cancer.

Temporal and spatial distributions of ozone in Atlanta: regulatory and epidemiologic implications.

Relationships between ambient levels of selected air pollutants and pediatric asthma exacerbation in Atlanta were studied retrospectively. As a part of this study, temporal and spatial distributions of ambient ozone concentrations in the 20-county. Atlanta metropolitan area during the summers of 1993, 1994, and 1995 were assessed. A universal kriging procedure was used for spatial interpolation of aerometric monitoring station data. In this paper, the temporal and spatial distributions of ozone are described, and regulatory and epidemiologic implications are discussed. For the study period, the Atlanta ozone nonattainment area based on the 1-h, exceedance-based standard of 0.12 ppm is estimated to expand--from 56% of the Atlanta MSA by area and 71% by population to 88% by area and 96% by population--under the new 8-h, concentration-based standard of 0.08 ppm. Regarding asthma exacerbation, a 4% increase in pediatric asthma rate per 20-ppb increase in ambient ozone concentration was observed (p-value = 0.001), with ambient ozone level representing a general indicator of air quality due to its correlations with other pollutants. The use of spatial ozone estimates in the epidemiologic analysis demonstrates the need for control of demographic covariates in spatiotemporal assessments of associations of ambient air pollutant concentrations with health outcome.

The issue of confounding in epidemiological studies of ambient air pollution and pregnancy outcomes.

BACKGROUND: Relationships between ambient air pollution levels during pregnancy and adverse pregnancy outcomes have been investigated using one of three analytic approaches: ambient pollution levels have been contrasted over space, time or both space and time. Although the three approaches share a common goal, to estimate the causal effects of pollution on pregnancy outcomes, they face different challenges with respect to confounding. METHODS: A framework based on counterfactual effect definitions to examine issues related to confounding in spatial, temporal, and spatial-temporal analyses of air pollution and pregnancy outcomes is presented, and their implications for inference are discussed. RESULTS: In spatial analyses, risk factors that are spatially correlated with pollution levels are confounders; the primary challenges relate to the availability and validity of risk factor measurements. In temporal analyses, where smooth functions of time are commonly used to control for confounding, concerns relate to the adequacy of control and the possibility that abrupt changes in risk might be systematically related to pollution levels. Spatial-temporal approaches are subject to challenges faced in both spatial and temporal analyses. CONCLUSION: Each approach faces different challenges with respect to the likely sources of confounding and the ability to control for that confounding because of differences in the type, availability, and quality of information required. Thoughtful consideration of these differences should help investigators select the analytic approach that best promotes the validity of their research.

Oils and cancer.

Epidemiologic evidence on the relationship between mineral oil exposure and cancer is reviewed. The review is restricted to occupations involving substantial dermal and inhalational exposure and for which an epidemiologic literature exists: metal machining, print press operating, and cotton and jute spinning. Mineral oils are complex mixtures of aliphatic hydrocarbons, naphthenics, and aromatics, the relative distribution of which depends on the source of the oil and the method of refinement. End-use products contain a variety of additives, and contamination by other agents generally occurs during use. Suspect agents include polycyclic aromatic hydrocarbons (PAH) (particularly benz[a]pyrene), nitrosamines, chlorinated paraffins, long-chain aliphatics, sulfur, N-phenyl-2-naphthylamine, and formaldehyde. The heterogeneity of this exposure makes epidemiologic study difficult and meta-analysis inappropriate. Nonetheless, several associations emerge from the literature with varying degrees of support. There is clear evidence that early formulations of mineral oils used in cotton and jute spinning and in metal machining were carcinogenic to the skin. Associations of mineral oil exposure with laryngeal and rectal cancer have received some support in the literature, particularly with respect to straight oils. Evidence is suggestive that grinding operations (which can entail either mineral oil-based or ethanolamine-based fluids) are associated with excess risk of cancer of the esophagus, stomach, and pancreas. A number of bladder cancer case-control studies have noted an association with work as a machinist. There is limited evidence of an association with cancer of the colon, prostate, and sinonasal region. Several studies of printers have yielded positive findings for lung cancer, whereas studies in metal machinists have been generally negative. The PAH and nitrosamine content of current formulations is lower than in the past and the implications of these changes in composition to the carcinogenicity of the formulations are not yet known.

Estimating occupational radiation doses when individual dosimetry information is not available: a job exposure matrix.

BACKGROUND: A job exposure matrix (JEM) was developed for a population based case control study to assess the possible association between occupational radiation and non-Hodgkin's lymphoma. METHODS: Using published radiation monitoring data, we developed a radiation JEM composed of estimated annual dose distributions, categorized by time period, for a broad range of occupational and industrial groups. RESULTS: When information is available to correctly assess an individual's exposure status, the annual dose distributions in the JEM can be used in conjunction with job histories to estimate the distribution of possible cumulative doses for individuals. The median of the cumulative dose distribution can then be used in standard epidemiologic analysis. In addition, methods can be applied that incorporate the uncertainty about each individual's true dose into risk estimates and associated confidence intervals. CONCLUSIONS: The JEM can be useful in estimating occupational radiation exposures in other studies, particularly population based case control studies which include detailed occupational histories.

Micronuclei and other nuclear anomalies in buccal smears: a field test in snuff users.

A revised protocol for the exfoliated cell micronucleus assay was field-tested in a population exposed to a genotoxic agent, snuff, at levels associated with a significant increase in cancer risk. The standard assay involves examination of epithelial smears to determine the prevalence of micronucleated cells, an indication of chromosome breakage or mitotic interference. The assay was revised to increase specificity and to include separate scoring of other nuclear anomalies associated with cytotoxicity and genotoxicity. The modified assay was applied to buccal smears of 38 female snuff users and 15 female nonusers recruited from a North Carolina clinic in 1987. The prevalence of micronucleation was elevated in the snuff users as compared with the nonusers (prevalence ratio = 2.4, 95% confidence interval 1.1-5.2) and, to a lesser extent, at the usual contact site as compared with a distal buccal site in the snuff users (prevalence ratio = 1.5, 95% confidence interval 0.9-2.5). The pattern of relative frequencies of several nuclear anomalies provided strong evidence of a cytotoxic effect, the prevalence ratios ranging from 2 to 13. Nuclear degenerative phenomena can be difficult to distinguish from classical micronuclei; thus, the observed association of indicators of cytotoxicity with exposure introduces the possibility of bias away from the null in micronucleus findings due to differential misclassification. Until methods to better distinguish extranuclear bodies of different origins become available, investigators should use the revised protocol and should focus on agents not thought to be cytotoxic.

Mortality studies of machining fluid exposure in the automobile industry I: A standardized mortality ratio analysis.

Machining fluids are widely used in a variety of common industrial metalworking operations to lubricate and cool both the tool and the working surfaces. Previous studies have suggested elevated respiratory, digestive, and skin cancers in exposed populations. This cohort study was initiated to assess whether long-term exposure to machining fluids in the course of machining, grinding, and other cutting operations is associated with excess cancer mortality. The cohort includes more than 45,000 automobile production workers from 3 plants, almost 1 million years of follow-up, over 10,000 deaths, and an extensive exposure assessment component. Standardized mortality ratios (SMRs) have been estimated for each of the 3 plants, using both U.S. as well as local populations as reference. Relative risks of 1.2-3.1 have been observed for several specific respiratory and digestive cancers of a priori interest, including cancer of the stomach, large intestine, pancreas, lung, and larynx. In addition, elevated risks for leukemia and asthma were noted. Future exposure-response analyses will provide the opportunity to identify relatively modest excesses in cause-specific mortality risk associated with exposure to specific types (straight, soluble, or synthetic), additives, or components of machining fluids.

Case-control assessment of the association between non-Hodgkin's lymphoma and occupational radiation with doses assessed using a job exposure matrix.

BACKGROUND: Epidemiologic data for an association between radiation exposure and non-Hodgkin's lymphoma (NHL) have been inconclusive though the strongest evidence has been provided by studies of patients treated with radiotherapy. METHODS: We evaluated the association between occupational radiation exposure and non-Hodgkin's lymphoma in men using a population-based case-control study with 1,056 case and 1,860 control subjects sampled from eight geographic areas in the United States. Because dosimetry data were not available, doses were estimated for individuals who reported occupational radiation exposure using a radiation job exposure matrix developed for this purpose. Conditional logistic regression was used to model the association between reported occupational radiation exposure and NHL incidence. RESULTS: We found that most men (> 90%) did not report exposure to occupational sources of radiation. Among those who reported exposure, estimated cumulative doses were low, with an estimated mean of less than 0.02 Gray and a maximum of 0.12 Gray. The risk for NHL was not associated with ever having reported an occupational radiation exposure (OR = 0.90, 95% CI = 0.74-1.10) nor was there evidence of a dose-response relationship between risk and either the estimated cumulative doses or duration of exposure. CONCLUSIONS: The findings in this study are consistent with results from most current research on occupational radiation and NHL risk that have found no increased risk of NHL at low levels of occupational radiation exposure. While it should be noted that exposure misclassification likely biased our results toward the null, this large population-based case-control study adds to existing evidence which suggests that there is little to no increased risk for NHL associated with exposure to low levels of radiation such as that commonly found in many occupational settings.

Relation of cigarette smoking to non-Hodgkin's lymphoma among middle-aged men.

Because of previous inconsistencies in the observed relation of cigarette smoking to non-Hodgkin's lymphoma, this association was investigated in the Selected Cancers Study, a population-based case-control study of 1,193 non-Hodgkin's lymphoma cases and 1,903 controls, conducted between 1984 and 1988. Study subjects were men, and the median age of non-Hodgkin's lymphoma cases was 50 years (range, 32-60 years). As compared with the risk among men who had never smoked cigarettes, the risk among ever smokers was not increased (odds ratio (OR) = 1.05, p approximately 0.50), but the risk was significantly elevated among men who reported smoking > or = 2 1/2 packs per day and among men who had smoked for 30-39 years (OR = 1.45 in each group, p < 0.05). The estimated odds ratio among the 350 heavy smokers (> or = 50 pack-years) was 1.41 (95% confidence interval 1.08-1.85) after controlling for educational achievement, various occupational and medical exposures, and other potential confounders. The observed associations, however, tended to vary by age, with the odds ratio among heavy smokers decreasing from 2.8 among 32- to 44-year-olds to 1.1 among men over 55 years of age. These age-related differences, which may account for some of the inconsistencies seen in previous studies of cigarette smoking and non-Hodgkin's lymphoma, should be considered in future investigations.