Ellen A. Eisen

Human papillomavirus 16 and head and neck squamous cell carcinoma

Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case–control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA. HPV16 seropositivity was associated with 1.5‐ and 6‐fold risks for tumors of the oral cavity and pharynx, respectively. There was a dose response trend for HPV16 titer and increasing risk of HNSCC (p < 0.0001) and HPV16 tumor DNA (p < 0.0001). In cases, HPV16 DNA and seropositivity were significantly associated with sexual activity; odds ratios (ORs) of 12.8 and 3.7 were observed for more than 10 oral sexual partners and ORs of 4.5 and 3.2 were associated with a high number of lifetime sexual partners, respectively. Finally, HPV16 seropositivity and HPV16 tumor DNA were associated with hazard ratios of 0.4 and 0.5, respectively, indicating better survival for HPV positive individuals. HPV16 seropositivity was associated with risk for HNSCC, with greatest risk for pharyngeal cancer. We observed dose response relationships between serology titer and both risk for HNSCC and HPV16 tumor DNA. In cases, HPV16 tumor DNA and positive serology were associated with sexual history and improved disease free survival.

RESPIRATORY HEALTH OF AUTOMOBILE WORKERS EXPOSED TO METAL-WORKING FLUID AEROSOLS: RESPIRATORY SYMPTOMS

A total of 1,811 automobile workers at three General Motors facilities were evaluated by questionnaire for possible respiratory effects resulting from airborne exposures to metal-working fluids (MWF): 1,042 currently worked as machinists and were exposed to one of three types of MWF aerosols (straight mineral oils, soluble oil emulsions, or water-based synthetic fluids that contained no oils); 769 assembly workers, without direct exposure, served as an internal reference group (of these, 239 had never worked as machinists). Symptoms of usual cough, usual phlegm, wheezing, chest tightness, and breathlessness, as well as physician-diagnosed asthma, and chronic bronchitis were the primary outcomes examined. Machinists as a whole had higher prevalence of cough, phlegm, wheezing, and breathlessness than that of assembly workers. Adjusting for confounding, phlegm and wheeze were associated with increasing levels of current exposure to straight oils; cough, phlegm, wheeze, chest tightness, and chronic bronchitis were associated with increasing levels of current exposure to synthetics. In models that included both past and current exposure, only current exposures to straight and synthetic fluids were associated with current symptoms.

Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies

OBJECTIVES Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. METHODS Six research groups collected prospective data at > 50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. RESULTS At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. CONCLUSIONS Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure-response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference.

Lung Cancer and Vehicle Exhaust in Trucking Industry Workers

Background An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. Objectives We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure. Methods Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey. Results Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. Conclusions Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer.

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2-7.5) among those with more than 1.4 mg/m3-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained.

The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head and neck associated with alcohol and tobacco use.

Alcohol consumption interacts with tobacco use to increase the risk of head and neck squamous cell carcinoma (HNSCC). Alcohol is eliminated through oxidation by alcohol dehydrogenase (ADH). The ADH1C gene is polymorphic and the ADH1C*1 allele metabolizes ethanol to acetaldehyde at a higher rate than the variant ADH1C*2 allele. This polymorphism has been reported to alter the risk of HNSCC associated with alcohol use, although the literature differs in the estimates of both the magnitude and direction of this effect modification. We have investigated the association between the established risk factors for HNSCC and variant genotypes of ADH1C in a case-control study in the greater Boston area. ADH1C genotypes were determined from 521 cases and 599 population-based controls. The odds ratio (OR) for HNSCC associated with >26 drinks per week was 3.7 [95% confidence interval (95% CI), 2.4-5.7], whereas the OR for smoking >58 pack-years was 5.6 (95% CI, 3.8-8.4). The combination of heavy smoking and heavy drinking significantly interacted to produce an OR of 17.3 (95% CI, 7.8-38.3). In cases and controls, respectively, 16% and 14% were ADH1C*1-1, 46% and 46% were ADH1C*1-2 and 38% and 40% were ADH1C*2-2. There was a significant interaction of alcohol use and genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1 (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI, 1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling for smoking, age, race, and gender). These findings suggest that the ADH1C*2-2 genotype is associated with susceptibility to smoking and drinking-related HNSCC by modifying the biologically effective dose of alcohol.

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers.

BackgroundTo better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM2.5 and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.MethodsTwenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM2.5 metal exposures both with and without adjustment for total PM2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM2.5 and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM2.5 as surrogates for the differential effects of metal exposures in models for night rMSSD.ResultsThe median PM2.5 exposure was 650 μg/m3; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m3 to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m3 increase in manganese. However, even after adjusting for individual metals, increases in total PM2.5 exposures were associated with declines in night rMSSD.ConclusionThese results support the cardiotoxicity of PM2.5 metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.

A case-crossover study of transient risk factors for occupational acute hand injury

Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work.

Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES.

Background We measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999–2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women’s regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999–2002). Results The eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05]. Conclusions Findings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and/or working in an agricultural area.

Cotton dust and endotoxin exposure and long-term decline in lung function : Results of a longitudinal study

BACKGROUND To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China. METHODS Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers--both active and retired--were identified for testing in the 11th year. Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin sampling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data. RESULTS The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be explained by worker selection or dropout. When cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline. CONCLUSIONS Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers.