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H Checkoway,
R M Ray,
J I Lundin,
G Astrakianakis,
N S Seixas,
J E Camp,
K J Wernli,
E D Fitzgibbons,
W Li,
Z Feng,
D L Gao,
D B Thomas
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ABSTRACT: Numerous epidemiological studies of lung cancer among textile workers worldwide consistently indicate reduced risks related to cotton dust exposure, presumably due to endotoxin contamination. Our objective was to investigate associations with other exposures potentially related to lung cancer, including wool and synthetic fibre dusts, formaldehyde, silica, dyes and metals, that have only been studied to a limited extent in the textile industry.
We conducted a case-cohort study nested within a cohort of 267,400 women textile workers in Shanghai, China. We compared work assignments and exposure histories of 628 incident lung cancer cases, diagnosed during 1989-1998, with those of a reference subcohort of 3188 workers. We reconstructed exposures with a job-exposure matrix developed specifically for textile factories. Cox proportional hazards modelling was applied to estimate age/smoking-adjusted relative risks (hazard ratios) and risk gradients associated with job assignments and specific agents other than cotton dust and endotoxin.
No associations were observed for lung cancer with wool, silk or synthetic fibre dusts, or with most other agents. However, increased risks, although statistically imprecise, were noted for ≥ 10 years' exposures to silica (adjusted HR 3.5, 95% CI 1.0 to 13) and ≥ 10 years' exposures to formaldehyde (adjusted HR 2.1, 95% CI 0.4 to 11).
Exposures to silica and formaldehyde, although not widespread among the cohort, may have increased lung cancer risk. Silica is an established human lung carcinogen, whereas there is only weak prior evidence supporting an association with formaldehyde. Both exposures warrant consideration as potential lung carcinogens in textile manufacturing.
Occupational and environmental medicine 12/2010; 68(6):425-9. · 3.64 Impact Factor
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ABSTRACT: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson's disease (PD), they typically have limited information for clinical diagnosis.
We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.
We identified 60 cases with prevalent PD (1.0%; 95% confidence interval, CI = 0.8-1.3%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95% CI = 0.26-0.95) and for those who smoked ≥50 pack-years (OR = 0.53; 95% CI = 0.29-0.96). Estimates for smoking were similar when ≥2 data sources were required. Estimates for self-report alone were attenuated towards null.
Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.
Neuroepidemiology 09/2010; 35(4):241-9. · 2.31 Impact Factor
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Eva Y Wong,
Ray Ray,
Dao L Gao,
Karen J Wernli,
Wenjin Li,
E Dawn Fitzgibbons,
Janice E Camp,
Patrick J Heagerty,
Anneclaire J De Roos,
Victoria L Holt,
David B Thomas, Harvey Checkoway
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ABSTRACT: Strenuous occupational physical activity and physical demands may be risk factors for adverse reproductive outcomes.
A retrospective study in the Shanghai, China textile industry study collected women's self-reported reproductive history. Occupational physical activity assessment linked complete work history data to an industry-specific job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression for the first pregnancy outcome and utilized generalized estimating equations to consider all pregnancies per woman.
Compared with women employed in sedentary jobs, a reduced risk of miscarriage was found for women working in jobs with either light (OR 0.18, 95% CI: 0.07, 0.50) or medium (OR 0.24, 95% CI: 0.08, 0.66) physical activity during the first pregnancy and over all pregnancies (light OR 0.32, 95% CI: 0.17, 0.61; medium OR 0.43, 95% CI: 0.23, 0.80). Frequent crouching was associated with elevated risk (OR 1.82, 95% CI: 1.14, 2.93; all pregnancies per woman).
Light/medium occupational physical activity may have reduced miscarriage risk, while specific occupational characteristics such as crouching may have increased risk in this cohort.
American Journal of Industrial Medicine 03/2010; 53(5):497-505. · 1.63 Impact Factor
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C E Furlong,
S M Suzuki,
R C Stevens,
J Marsillach,
R J Richter,
G P Jarvik, H Checkoway,
A Samii,
L G Costa,
A Griffith,
J W Roberts,
D Yearout,
C P Zabetian
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ABSTRACT: Human paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that exhibits a broad substrate specificity. In addition to protecting against exposure to some organophosphorus (OP) pesticides by hydrolyzing their toxic oxon metabolites, PON1 is important in protecting against vascular disease by metabolizing oxidized lipids. Recently, PON1 has also been shown to play a role in inactivating the quorum sensing factor N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) of Pseudomonas aeruginosa. Native, untagged engineered recombinant human PON1 (rHuPON1) expressed in Escherichia coli and purified by conventional column chromatographic purification is stable, active, and capable of protecting PON1 knockout mice (PON1(-/-)) from exposure to high levels of the OP compound diazoxon. The bacterially derived rHuPON1 can be produced in large quantities and lacks the glycosylation of eukaryotic systems that can produce immunogenic complications when inappropriately glycosylated recombinant proteins are used as therapeutics. Previous studies have shown that the determination of PON1 status, which reveals both PON1(192) functional genotype and serum enzyme activity level, is required for a meaningful evaluation of PON1's role in risk of disease or exposure. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates, allowing for use of this protocol in non-specialized laboratories. Factors were also determined for inter-converting rates of hydrolysis of different substrates. PON1 status also plays an important role in revealing changes in HDL-associated PON1 activities in male patients with Parkinson disease (PD). Immunolocalization studies of PONs 1, 2 and 3 in nearly all mouse tissues suggest that the functions of PONs 1 and 3 extend beyond the plasma and the HDL particle.
Chemico-biological interactions 03/2010; 187(1-3):355-61. · 2.46 Impact Factor
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ABSTRACT: To determine if work area measurements of endotoxin and/or cotton dust obtained from the vertical elutriator (VE) can be used to predict levels of personal endotoxin exposure as measured by the Institute of Occupational Medicine (IOM) inhalable dust sampler in the cotton textile industry.
Fifty-six work area cotton dust samples were collected from 14 areas and 82 personal cotton dust samples were collected from 41 workers in three textile mills (Mills A, B and C) in Shanghai, China. Cotton dust concentrations were determined gravimetrically from sample filters, of which endotoxin concentrations were determined using a kinetic chromogenic modification of the limulus amoebocyte lysate assay. Linear regression models were used to determine the association between log IOM personal endotoxin concentration and log VE area endotoxin concentration.
Median cotton dust and endotoxin concentrations measured from VE area samples in the three mills were 0.36 mg m(-3) and 1280.76 endotoxin units per cubic meter (EU m(-3)), respectively, compared to 1.74 mg m(-3) and 2226.83 EU m(-3) from IOM personal samples. Excluding samples from weaving processes, we observed linear associations between VE area measures of endotoxin and IOM personal endotoxin concentrations; VE area concentration of endotoxin explained 83 and 89% of the total variation in IOM personal endotoxin concentration for Mills A and B, respectively (Mill A: R2 = 0.83, P < 0.0001; Mill B: R2 = 0.89, P < 0.0001). Although area measures of cotton dust was also a significant predictor of person endotoxin, the model explained less of the variance in personal endotoxin measurements.
Specific to the conditions of the textile mills investigated in this study, work area measurements of endotoxin, but not cotton dust, may be reasonable proxies for personal levels, at least for rank-ordering exposures.
Annals of Occupational Hygiene 01/2008; 52(1):45-54. · 1.95 Impact Factor
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ABSTRACT: Cement masons are known to have significant silica exposure, and silica exposure and silicosis are thought to increase risk of autoimmune disease. Because the mechanisms remain obscure, with inconclusive reports of systemic immune effects following silica exposure, our goal was to identify potential early markers of silica-related immunologic and respiratory effects.
We conducted a cross-sectional study of cement mason apprentices and electrician (control) apprentices. Demographics, dust exposure history, symptoms, spirometry, exhaled nitric oxide, and blood (for immunoglobulins, cytokines, cell counts, and surface markers) were obtained from 11 cement mason apprentices and a comparison group of 21 electrician apprentices.
Masons had significantly higher (P < 0.05) masonry dust exposure (42 versus 9 dust-hour-years), serum interleukin-1beta (IL-1beta; 12 versus 9 pg/ml), IL-2 (20 versus 8 pg/ml), IL-4 (193 versus 67 pg/ml), IL-10 (44 versus 21 pg/ml), and interferon-gamma (139 versus 65 pg/ml) compared with electricians. In contrast, masons had significantly lower percentages of CD25+ (12% versus 20%) and CD69+ (4% versus 9%) lymphocytes.
Mason apprentices had higher levels of serum proinflammatory cytokines and lower percentages of CD25+ and CD69+ lymphocytes than did electrician apprentices. These preliminary findings suggest that mason apprentices may be at greater risk of a systemic proinflammatory state that is potentially linked to immune dysregulation. Although distinct limitations of this preliminary data are recognized, this is consistent with early biologic effects leading to increased incidence of autoimmune disease among silica-exposed workers. Prospective studies are needed to validate these initial findings and clarify the temporal sequence of observed relationships.
Arthritis & Rheumatism 02/2007; 57(1):147-53. · 7.87 Impact Factor
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W Li,
R M Ray,
D L Gao,
E D Fitzgibbons,
N S Seixas,
J E Camp,
K J Wernli,
G Astrakianakis,
Z Feng,
D B Thomas, H Checkoway
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ABSTRACT: To investigate whether occupational exposures to dusts and chemicals in the Shanghai textile industry are associated with risk of pancreatic cancer.
A case cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China was conducted among 180 incident pancreatic cancer cases and an age stratified randomly selected comparison subcohort (n = 3188). A complete occupational history of work in the textile industry was obtained for each woman, and was linked to a job exposure matrix developed for the textile industry to estimate exposures to specific dusts and chemicals. Cumulative exposures to cotton dust and endotoxin were reconstructed from historical and contemporaneous measurements.
After adjusting for smoking status, a trend of decreasing risk of pancreatic cancer was observed for increasing cumulative exposures to cotton dust and endotoxin with a lag of 20 years. The hazard ratios for women cumulatively exposed to >143.4 mg/m3 x years of cotton dust and >3530.6 EU/m3 x years of endotoxin were 0.6 (95% CI 0.3 to 0.9) and 0.5 (95% CI 0.3 to 0.9), respectively, compared to unexposed women. There was little evidence that exposures to other textile dusts and chemicals were associated with risk of pancreatic cancer.
Occupational exposure to cotton dust and endotoxin in the textile industry may have reduced risks of pancreatic cancer in this cohort. These associations should be replicated by others before making a firm conclusion of their possible effects on pancreatic cancer.
Occupational and environmental medicine 12/2006; 63(12):788-93. · 3.64 Impact Factor
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ABSTRACT: Thyroid cancer risk has been previously associated with increased age at first pregnancy and history of miscarriage. Occupational risk factors for thyroid cancer, with the exception of radioactive iodine, have not been well investigated. We conducted a case-cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China, who had been followed for cancer incidence during 1989-1998.
The analysis included 130 incident thyroid cases and 3,187 subcohort non-cases. Reproductive history was determined by questionnaire at baseline. Historical exposures were reconstructed from work history and information on factory processes and exposures. Cox proportional hazards analysis was performed to estimate hazard ratios (HR) for reproductive factors and occupational exposures.
Associations were observed between thyroid cancer and employment in jobs with 10 or more years of benzene exposure (HR 6.43, 95% CI: 1.08, 38) and formaldehyde exposure (HR 8.33, 95% CI: 1.16, 60). Administration workers also had an increased risk (HR 1.56, 95% CI: 1.08, 2.25). No associations between examined reproductive factors and thyroid cancer were observed in this study.
Despite statistically imprecise risk estimates, the findings suggest potential associations with some occupational chemical exposures in this cohort of textile workers.
Archiv für Gewerbepathologie und Gewerbehygiene 04/2006; 79(3):251-8. · 1.89 Impact Factor
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W Li,
R M Ray,
D L Gao,
E D Fitzgibbons,
N S Seixas,
J E Camp,
K J Wernli,
G Astrakianakis,
Z Feng,
D B Thomas, H Checkoway
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ABSTRACT: To investigate whether occupational exposure to dusts and chemicals in the Chinese textile industry are associated with risk of nasopharyngeal cancer.
Sixty seven nasopharyngeal carcinoma (NPC) cases identified during 1989-98 and a random sample (n = 3188) of women were included in a case cohort study nested in a cohort of 267,400 women textile workers in Shanghai, China. A complete occupational history of work in the textile industry was obtained for each woman. A job exposure matrix developed by experienced industrial hygienists was used to assess exposures to specific dusts and chemicals.
Risk of NPC is associated with cumulative exposure to cotton dust. The hazard ratio for women cumulatively exposed to >143.4 mg/m3 x years of cotton dust was 3.6 (95% CI 1.8 to 7.2) compared with unexposed women. Trends of increasing risk were also found with increasing duration of exposure to acids and caustics (p = 0.05), and with years worked in dyeing processes (p = 0.06). Women who worked at least 10 years in dyeing processes had a 3.6-fold excess risk of NPC (95% CI 1.0 to 12.1).
Occupational exposure to cotton dust, acids, and caustics, and work in dyeing and printing jobs in the textile industry may have increased risk of NPC in this cohort.
Occupational and environmental medicine 02/2006; 63(1):39-44. · 3.64 Impact Factor
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ABSTRACT: Previous studies have suggested increased risks of colorectal cancers among textile industry workers, potentially related to synthetic fibers. To investigate risks of colon and rectum cancers in relation to these and other textile industry exposures, we conducted a case-cohort study nested within a cohort study of female employees from the Shanghai Textile Industry Bureau (STIB). Cox proportional hazard regression modeling was used to estimate hazard ratios (HR) for colon and rectum cancers associated with duration of employment (e.g., 0, >0 to <10, 10 to <20 years, > or =20 years) in various jobs classified according to process type and exposures to specific agents. Our findings indicate that certain long term exposures may pose increased risk of colorectal cancers, especially dyes and dye intermediates with colon cancer (> or =20 years exposure versus never, HR=3.9; 95% CI: 1.4-10.6), and maintenance occupation (HR = 2.3; 95% CI: 1.0-5.7) and metals exposure (HR = 2.0; 95% CI: 1.1-3.6) with rectum cancer. A decreased risk of rectum cancer was associated with exposure to natural fibers such as cotton (HR = 0.7; 95% CI: 0.5-0.9), and a trend of decreasing rectum cancer incidence was observed by category of cumulative quantitative cotton dust or endotoxin exposures, when exposures were lagged by 20 years.
Cancer Causes and Control 12/2005; 16(10):1177-88. · 2.88 Impact Factor
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ABSTRACT: Occupational exposure to animals or the public could result in exposure to infectious agents, which may play a role in the aetiology of lymphohaematopoietic (LH) cancers.
To conduct a population based, case-control study of death certificate data from 1984 to 1998 in 24 US states in order to evaluate the risk of mortality from LH neoplasms associated with occupational exposure to animals or the public.
Cases were selected as those with an underlying cause of death of non-Hodgkin's lymphoma (NHL, n = 72,589), Hodgkin's disease (HD, n = 5479), multiple myeloma (n = 35,857), or leukaemia (n = 68,598); 912 615 controls were randomly selected from all remaining deaths, frequency matched on age, sex, race, and geographic region.
Occupational exposure to animals was associated with modest increased risks of mortality from all four LH cancers; these associations varied by region. Occupational exposure to the public was associated with only negligible increased risk with LH cancer outcomes. Occupations involving animal exposure were predominantly agricultural, and the risks associated with employment in the livestock industry exceeded the corresponding risks associated with the crop industry for all outcomes except HD.
Increased risks of NHL, HD, multiple myeloma, and leukaemia were associated with occupations that involved animal exposure. Regional differences in risk imply that the risks may be associated with exposure to specific livestock or farming practices. However, these associations may be confounded by other farming related exposures, such as pesticides. Because the use of death certificates to classify occupation may result in misclassification during aetiologically relevant time periods, these hypotheses should be further explored in studies with detailed information on lifetime occupation.
Occupational and environmental medicine 11/2005; 62(10):726-35. · 3.64 Impact Factor
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ABSTRACT: To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed to silica in California's diatomaceous earth industry. To encourage application of this approach, computer code is provided.
Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations.
The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well.
This flexible statistical approach reduces the dependence on a priori assumptions, while pointing to a suitable parametric model if one exists. In the absence of an appropriate parametric form, however, splines can provide exposure-response information useful for aetiological research and public health intervention.
Occupational and environmental medicine 11/2004; 61(10):854-60. · 3.64 Impact Factor
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ABSTRACT: A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates.
An ISAAC questionnaire with supplemental questions on environmental variables was distributed to 5495 school children in Hanoi and a suburban district, Dong Anh. The response rate was 65.7%.
In Dong Anh, the following were among the significant age and gender adjusted associations: pig ownership [odds ratio (OR) (95% confidence interval), OR = 1.79 (1.18-2.70) for doctor-diagnosed asthma (DDA), OR = 1.72 (1.08-2.78) for doctor diagnosed hay fever (DDHF)] and farming [OR = 1.67 (1.27-2.19) for ever asthma, OR = 1.51 (1.09-2.09) for DDHF]. In multivariate models, tuberculosis (TB) was a significant predictor of atopic symptoms [Hanoi: OR = 3.09 (1.10-8.70) for DDA, Dong Anh: OR = 3.71 (1.40-9.84) for DDA, OR = 4.66 (1.88-11.57) for DDHF].
These findings are contrary to the "hygiene hypothesis". Recent immunologic and epidemiologic studies refute the inverse association between allergy and TB and may be one explanation for the positive association in this study. The positive association with pig ownership and farming may be because of exposures on farms in a developing country that may be different from exposures in farms of developed countries.
Allergy 07/2004; 59(6):637-44. · 6.27 Impact Factor
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ABSTRACT: Dietary influences on oxidative stress have been thought to play important role in the etiology of PD.
To examine associations of PD with dietary nutrients, including minerals, vitamins, and fats.
A population-based case-control study was conducted among newly diagnosed case (n = 250) and control subjects (n = 388) identified between 1992 and 2002 from enrollees of the Group Health Cooperative health maintenance organization in western Washington state. Controls were frequency matched to cases on sex and age. In-person interviews elicited data on food frequency habits during most of adult life. Nutrient intakes were calculated and analyzed by adjusting each person's nutrient intake by their total energy intake (the nutrient density technique).
Subjects with an iron intake in the highest quartile compared with those in the lowest quartile had an increased risk of PD (odds ratio = 1.7, 95% CI: 1.0, 2.7, trend p = 0.016). There was an apparent joint effect of iron and manganese; dietary intake above median levels of both together conferred a nearly doubled risk compared with lower intakes of each nutrient (odds ratio = 1.9, 95% CI: 1.2, 2.9). No strong associations were found for either antioxidants or fats.
A high intake of iron, especially in combination with high manganese intake, may be related to risk for PD.
Neurology 07/2003; 60(11):1761-6. · 8.31 Impact Factor
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S N Kelada,
P Costa-Mallen, H Checkoway,
H A Viernes,
F M Farin,
T Smith-Weller,
G M Franklin,
L G Costa,
W T Longstreth,
C E Furlong,
G P Jarvik,
P D Swanson
Journal of Neurology Neurosurgery & Psychiatry 05/2003; 74(4):546-7. · 4.76 Impact Factor
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ABSTRACT: The authors studied the association between incidence of primary cardiac arrest and daily measures of fine particulate matter (</=2.5 micro m) using a case-crossover study of 1,206 Washington State out-of-hospital cardiac arrests (1985-1994) among persons with (n = 774) and without (n = 432) clinically recognized heart disease. The authors compared particulate matter levels on the day of the cardiac event and the 2 days preceding the event with levels from matched reference days. The estimated relative risk for a 13.8- micro g/m(3) increase in fine particulate matter (nephelometry: 0.54 x 10(-1) km(-1 )bsp) on the day prior to cardiac arrest was 0.94 (95% confidence interval: 0.88, 1.02). Pollutant levels measured on the same day as the event and on the 2 days preceding the event demonstrated similar results. No increased risk was found among all cases with preexisting cardiac disease (odds ratio = 0.97, 95% confidence interval: 0.89, 1.07); however, an unexpected association appeared between current smokers with preexisting heart disease and increased particulate matter levels 2 days prior to the event (odds ratio = 1.29, 95% confidence interval: 1.06, 1.55). This association was not present in the 0- or 1-day lag analyses or in persons with other diseases. There was no consistent association between increased levels of fine particulate matter and risk of primary cardiac arrest.
American Journal of Epidemiology 03/2003; 157(6):501-9. · 5.22 Impact Factor
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ABSTRACT: To study the relation between exposure to crystalline silica and silicosis mortality. Although mortality is an important endpoint for regulators, there have been no exposure-response studies for silicosis mortality, because of the relative rareness of silicosis as an underlying cause of death, and the limited availability of quantitative exposure estimates.
Data from six occupational cohorts were pooled with good retrospective exposure data in which 170 deaths from silicosis were reported. Standard life table analyses, nested case-control analyses, and risk assessment were performed.
The rate of silicosis mortality in the combined data was 28/100 000 py, increasing in nearly monotonic fashion from 4.7/100 000 for exposure of 0-0.99 mg/m(3)-years to 233/100 000 for exposure of >28.1 mg/m(3)-years. The estimated risk of death up to age 65 from silicosis after 45 years of exposure at 0.1 mg/m(3) silica (the current standard in many countries) was 13 per 1000, while the estimated risk at an exposure of 0.05 mg/m(3) was 6 per 1000. Both of these risks are above the risk of 1 per 1000 typically deemed acceptable by the US OSHA.
The findings from this pooled analysis add further support to the need to control silica exposure and to lower the occupational standards. Our estimates of lifetime silicosis mortality risk are probably underestimates as, in addition to exposure misclassification, our study might have suffered from outcome misclassification in that silicosis deaths might have been coded to other related causes, such as tuberculosis or chronic obstructive pulmonary disease.
Occupational and Environmental Medicine 11/2002; 59(11):723-8. · 3.02 Impact Factor
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ABSTRACT: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele.
The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian.
The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes.
The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.
Neurology 06/2002; 58(9):1381-7. · 8.31 Impact Factor
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ABSTRACT: To estimate excess lifetime risk of (a) mortality from lung disease other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from occupational exposure to respirable crystalline silica dust.
Data from a cohort of California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson regression methods with internal and external adjustments for potential confounding by calendar time, age, smoking, Hispanic ethnicity, and time since first observation. Model fit was evaluated by comparing deviances and fitting cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis were estimated up to age 85 with an actuarial approach accounting for competing causes of death.
For deaths due to LDOC, a linear relative rate model gave the best fit in Poisson regression analyses. At the mean cumulative exposure of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio was 18.4. The excess lifetime risk for white men exposed to respirable cristobalite dust for 45 years at the current permissible exposure limit (PEL; about 0.05 mg/m(3)) of the Occupational Safety and Health Administration was 54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of radiographic silicosis largely manifest before the end of employment, the best fit was also the linear relative rate model, predicting a rate ratio of 25.6 for silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess lifetime risk for silicosis at the current PEL was 75/1000.
Current occupational health standards for crystalline silica permit risks of lung disease other than cancer far in excess of what is usually considered acceptable by the Occupational Safety and Health Administration (a lifetime risk of less than one in a thousand deaths).
Occupational and Environmental Medicine 02/2002; 59(1):36-43. · 3.02 Impact Factor
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F M Farin,
P Janssen,
S Quigley,
D Abbott,
C Hassett,
T Smith-Weller,
G M Franklin,
P D Swanson,
W T Longstreth,
C J Omiecinski, H Checkoway
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ABSTRACT: Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxides are potentially reactive intermediates formed through the oxidative metabolism of both exogenous and endogenous substances that contribute to cytotoxic damage mediated by oxidative stress. The microsomal (EPHX1) and soluble (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interindividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association between the risk of Parkinson's disease and genetic variation within the EPHX1 and EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to identify the allelic status of individuals with respect to specific single nucleotide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 of the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idiopathic Parkinson's disease patients and 212 control subjects matched on age, gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease.
Pharmacogenetics 12/2001; 11(8):703-8.
