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Biomedical subjects

J A Hoppin

Publications and source records attributed to J A Hoppin.

At least 19 recordsLinked to original sources

Fertility and exposure to solvents among families in the Agricultural Health Study.

BACKGROUND: Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility. OBJECTIVES: To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort. METHODS: The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples (wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112). RESULTS: Twenty eight per cent of the couples were defined as subfertile (not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios (OR) for exposure to solvents were calculated with logistic regression. Female (OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents (OR 1.21 (95% CI 0.93 to 1.57) for monthly exposure and 1.40 (95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure (either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility (OR 1.62 (95% CI 1.20 to 2.17) and OR 2.10 (95% CI 1.22 to 3.60), respectively). CONCLUSIONS: Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects.

Adult↗

Disease and injury among participants in the Agricultural Health Study.

The Agricultural Health Study (www.aghealth.org) is a cohort of 89,658 pesticide applicators and their spouses from Iowa and North Carolina assembled between 1993 and 1997 to evaluate riskfactorsfor disease in ruralfarm populations. This prospective study is just now reaching sufficient maturity for analysis of many disease endpoints. Nonetheless, several analyses have already provided interesting and important leads regarding disease patterns in agricultural populations and etiologic clues for the general population. Compared to the mortality experience of the general population in the two states (adjusted for race, gender, age and calendar time), the cohort experienced a very low mortality rate overall and for many specific causes and a low rate of overall cancer incidence. A few cancers, however, appear elevated, including multiple myeloma and cancers of the lip, gallbladder, ovary, prostate, and thyroid, but numbers are small for many cancers. A study of prostate cancer found associations with exposure to several pesticides, particularly among individuals with a family history of prostate cancer. Links to pesticides and other agricultural factors have been found for injuries, retinal degeneration, and respiratory wheeze. Methodological studies have determined that information collected by interview is unbiased and reliable. A third round of interviews scheduled to begin in 2005 will collect additional information on agricultural exposures and health outcomes. The study can provide data to address many health issues in the agricultural community. The study investigators welcome collaboration with interested scientists.

Accidents, Occupational↗

Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking.

BACKGROUND: Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers. AIMS: To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers. METHODS: Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994-97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers. RESULTS: Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR(dairy) = 1.26; OR(eggs) = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR(eggs) was 2.88 among past smokers but only 1.46 for never smokers. The OR(eggs) for current smokers of 0.80 might reflect self selection of exposure among smokers. CONCLUSIONS: Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.

Adolescent↗

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.

Adult↗

Occupational exposure to chlorophenol and the risk of nasal and nasopharyngeal cancers among U.S. men aged 30 to 60.

BACKGROUND: Elevated rates of nasal and nasopharyngeal cancers have been associated with wood-related occupational exposures, including chlorophenols, formaldehyde, and wood dust. METHODS: Occupational information was obtained from 43 nasal carcinoma cases, 92 nasopharyngeal carcinoma cases, and 1909 controls, by interview. Exact conditional logistic regression was used to evaluate the association of these cancers with chlorophenol exposure, estimated from a review of verbatim responses. RESULTS: Both nasal and nasopharyngeal cancers were significantly associated with estimated duration of chlorophenol exposure. For nasopharyngeal cancer, elevated risk was observed among those who held jobs assigned medium or high intensity chlorophenol exposure (n(exposed)=18, OR=1.94, 95% CI=1.03-3.50) and among those with 10+ years in jobs assigned high intensity with high certainty (n(exposed)=3, OR=9.07, 95% CI=1.41-42. 9). Controlling for estimated formaldehyde and wood dust exposure did not alter these findings, as much of the estimated chlorophenol exposure was among machinists. CONCLUSIONS: These findings support the hypothesis that occupational exposure to chlorophenol is a risk factor for nasal and nasopharyngeal cancer, although the role of machining-related exposures warrants further assessment.

Adult↗

Measurement variability associated with KXRF bone lead measurement in young adults.

In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 microg Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 microg Pb/g bone mineral SD = 2.5 and 2.0 microg Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 microg Pb/g bone mineral (SD = 2.6) and 6.0 microg Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed.

Adolescent↗

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.

Adult↗

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.

Aged↗

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.

Adenocarcinoma↗

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.

Adult↗

Occupational risk factors for sarcoma subtypes.

Herbicides, chlorophenols, and other occupational exposures are suspected risk factors for soft-tissue sarcoma, but the epidemiologic evidence is inconsistent. Given that soft-tissue sarcomas represent a heterogeneous mix of cancer subtypes and that these subtypes have different disease patterns by race, sex, and age at diagnosis, studying all soft-tissue sarcomas combined may mask subtype-specific associations. Using the Selected Cancers Study, a large population-based case-control study of sarcoma conducted among U.S. men aged 30 to 60 in 1984 to 1988, we explored the occupational risk factors for soft-tissue sarcoma subtypes and skeletal sarcoma. The analysis included 251 living sarcoma cases (48 dermatofibrosarcoma protuberans, 32 malignant fibrohistiocytic sarcoma, 67 leiomyosarcoma, 53 liposarcoma, and 51 skeletal sarcoma) and 1908 living controls. Exact conditional logistic regression models suggested patterns of subtype specificity for occupational exposures. Self-reported herbicide use was associated with malignant fibrohistiocytic sarcoma (OR = 2.9, 95% CI = 1.1-7.3). We found elevated risks for chlorophenol exposure and cutting oil exposure and malignant fibrohistiocytic sarcoma and leiomyosarcoma. We found no occupational risk factor for liposarcoma. Polytomous regression models identified different odds ratios across subtypes for plywood exposure and exposure to wood and saw dust. Although exploratory, this analysis suggests that occupational risk factors for sarcoma are not uniform across subtypes.

Adult↗

Occupational chlorophenol exposure and soft tissue sarcoma risk among men aged 30-60 years.

To evaluate the association of chlorophenol exposure with soft tissue sarcoma risk independent of phenoxyherbicide exposure, the authors analyzed data from the Selected Cancers Study, a population-based case-control study that included 295 male soft tissue sarcoma cases, aged 32-60 years, from eight population-based cancer registries and 1,908 male controls. Chlorophenol exposure was assigned using both an intensity and a confidence estimate by an industrial hygienist based on verbatim job descriptions. Seventeen percent of the jobs rated as high intensity involved wood preservation, while 82% involved cutting oils. Soft tissue sarcoma risk, modeled using conditional logistic regression, was significantly associated with ever having high-intensity chlorophenol exposure (odds ratio = 1.79, 95% confidence interval 1.10-2.88). A duration-response trend was evident among more highly exposed subjects (p for trend < 0.0001). For subjects with 10 or more years of substantial exposure, the odds ratio was 7.78 (95% confidence interval 2.46-24.65). These results suggest that chlorophenol exposure independent of phenoxyherbicides may increase the risk of soft tissue sarcoma. Because of the large number of machinists in the exposed group and the complex composition of cutting fluids, it is possible that another exposure involved in machining is responsible for the observed excess risk.

Adult↗

Use of a life events calendar approach to elicit occupational history from farmers.

BACKGROUND: Precise and valid exposure assessment is generally the primary challenge in retrospective occupational epidemiology studies, particularly when the only available method for exposure characterization is a personal interview. Agricultural workers may represent a particular challenge; for example, whereas many farmers have worked from childhood at the same location, raising the same crops and animals, they may have used different equipment, chemicals, and protective gear over time. One method to assist in recall is the "life events calendar," a cognitive tool based on the subject's own life history to help anchor occupational activities in time. METHODS: Unstructured interviews of farmers, focus groups, and pilot interviews among rural men, primarily African-Americans, were conducted to create a questionnaire for obtaining farm history information within the context of personal life events. RESULTS: Farmers used both personal events and national events (as well as events relating directly to farming) to recall their activities. These subjects had extensive history of farming (10-75 years) and chemical use (median lifetime chemicals = 13). CONCLUSION: The life events calendar provided a useful tool to facilitate the recall of a lifetime of agricultural activity. Life events calendars are useful additions to the tools available for retrospective occupational exposure assessment.

Adult↗

Validation of a self-administered lead exposure questionnaire among suburban teenagers.

Teenagers represent a unique population in which to evaluate lead exposure. A self-administered questionnaire was developed to evaluate the current and historic lead exposures of teenagers. This work evaluates the exposure questionnaire for both its ability to predict lead exposure and the accuracy of the teenage respondents. Subjects received the survey at school and were instructed to get assistance from their parents in questionnaire completion. Environmental samples (dust, soil, and water) were collected from 30 suburban Boston homes to evaluate the questionnaire's predictiveness. To evaluate the accuracy of subjects' responses, independent information about housing was obtained. The questionnaire was effective in identifying predictors of dust and soil lead levels, but not for water lead levels. Fine dust lead loading (< 150 microns) varied significantly among the six housing age categories (pre-1940, 1940-1949, 1950-1959, 1960-1969, 1970-1979, and > 1979) and traffic levels. Fine dust lead concentrations varied significantly with decade of housing construction. Mean soil lead levels varied significantly among housing age categories, traffic levels, and exterior construction materials. For the important predictors, there was excellent agreement between the teenagers' self-report and confirmatory information. For housing age categories, the observed agreement was 69%; for traffic level, the observed agreement was 88%. These results illustrate that questionnaires continue to be useful in evaluating home lead levels even in suburban homes and that teenagers are accurate respondents.

Adolescent↗

In vivo bone lead measurement in suburban teenagers.

OBJECTIVE: Bone represents a biologically active long-term storage site for lead, and bone lead data on teenagers are limited. Therefore, this study was designed to identify the distribution of bone lead in a teenage population and to explore the environmental and demographic factors associated with bone lead concentrations in young, nonoccupationally exposed subjects. DESIGN: A cross-sectional study of bone lead levels in high school students. PARTICIPANTS: A total of 168 students at a suburban Boston high school. Subjects (90 boys, 78 girls) ranged in age from 13.5 to 19 years and included 40% nonwhite minorities. Of the 168 subjects, 45 lived in homes constructed before 1960. None of the participants reported a history of lead poisoning. OUTCOME MEASURES: Tibial bone lead concentrations were measured in vivo for 60 minutes using K x-ray fluorescence. Lead exposure information was obtained by self-administered questionnaire. RESULTS: Point estimates of bone lead levels ranged from -7.15 to 14.23 microg lead/g bone mineral (microg/g), (mean, 4.0 microg/g; standard deviation, 4.4 microg/g). The reported measurement uncertainties accompanying each of the point estimates ranged from 2.56 to 9.01 microg/g (mean, 3.9 microg/g; standard deviation, 1.0 microg/g). Bone lead levels were not associated with the demographic factors of age, sex, or race. Additionally, current home conditions (housing age, traffic level) were not predictive of bone lead levels, even though these factors were predictive of in-home lead concentrations. CONCLUSIONS: These results demonstrate that although bone lead levels are measurable in this age group, the common predictors of blood and bone lead concentrations are not explanatory for bone lead levels.

Adolescent↗

Upper airway response in workers exposed to fuel oil ash: nasal lavage analysis.

OBJECTIVES: Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS: A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS: Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION: A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.

Adult↗