Glutathione S-Transferase Polymorphisms,Passive Smoking,Obesity, and Heart Rate Variability in Nonsmokers

Background

Disturbances of heart rate variability (HRV) may represent one pathway by which second-hand smoke (SHS) and air pollutants affect cardiovascular morbidity and mortality. The mechanisms are poorly understood.

Objectives

We investigated the hypothesis that oxidative stress alters cardiac autonomic control. We studied the association of polymorphisms in oxidant-scavenging glutathione S-transferase (GST) genes and their interactions with SHS and obesity with HRV.

Methods

A total of 1,133 nonsmokers > 50 years of age from a population-based Swiss cohort underwent ambulatory 24-hr electrocardiogram monitoring and reported on lifestyle and medical history. We genotyped GSTM1 and GSTT1 gene deletions and a GSTP1 (Ile105Val) single nucleotide polymorphism and analyzed genotype–HRV associations by multiple linear regressions.

Results

Homozygous GSTT1 null genotypes exhibited an average 10% decrease in total power (TP) and low-frequency-domain HRV parameters. All three polymorphisms modified the cross-sectional associations of HRV with SHS and obesity. Homozygous GSTM1 null genotypes with > 2 hr/day of SHS exposure exhibited a 26% lower TP [95% confidence interval (CI), 11 to 39%], versus a reduction of −5% (95% CI, −22 to 17%) in subjects with the gene and the same SHS exposure compared with GSTM1 carriers without SHS exposure. Similarly, obese GSTM1 null genotypes had, on average, a 22% (95% CI, 12 to 31%) lower TP, whereas with the gene present obesity was associated with only a 3% decline (95% CI, −15% to 10%) compared with nonobese GSTM1 carriers.

Conclusions

GST deficiency is associated with significant HRV alterations in the general population. Its interaction with SHS and obesity in reducing HRV is consistent with an impact of oxidative stress on the autonomous nervous system.     

A Systematic Review and Meta-analysis of Childhood Leukemia and Parental Occupational Pesticide Exposure

Objectives

We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.

Data sources

Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.

Data extraction

Two authors independently abstracted data and assessed the quality of each study.

Data synthesis

Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).

Conclusions

Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.     

Iron Metabolism Genes,Low-Level Lead Exposure,and QT Interval

Background

Cumulative exposure to lead has been shown to be associated with depression of electrocardiographic conduction, such as QT interval (time from start of the Q wave to end of the T wave). Because iron can enhance the oxidative effects of lead, we examined whether polymorphisms in iron metabolism genes [hemochromatosis (HFE), transferrin (TF) C2, and heme oxygenase-1 (HMOX-1)] increase susceptibility to the effects of lead on QT interval in 613 community-dwelling older men.

Methods

We used standard 12-lead electrocardiograms, K-shell X-ray fluorescence, and graphite furnace atomic absorption spectrometry to measure QT interval, bone lead, and blood lead levels, respectively.

Results

A one-interquartile-range increase in tibia lead level (13 μg/g) was associated with a 11.35-msec [95% confidence interval (CI), 4.05–18.65 msec] and a 6.81-msec (95% CI, 1.67–11.95 msec) increase in the heart-rate–corrected QT interval among persons carrying long HMOX-1 alleles and at least one copy of an HFE variant, respectively, but had no effect in persons with short and middle HMOX-1 alleles and the wild-type HFE genotype. The lengthening of the heart-rate–corrected QT interval with higher tibia lead and blood lead became more pronounced as the total number (0 vs. 1 vs. ≥2) of gene variants increased (tibia, p-trend = 0.01; blood, p-trend = 0.04). This synergy seems to be driven by a joint effect between HFE variant and HMOX-1 L alleles.

Conclusion

We found evidence that gene variants related to iron metabolism increase the impacts of low-level lead exposure on the prolonged QT interval. This is the first such report, so these results should be interpreted cautiously and need to be independently verified.     

Occupational exposure to power frequency magnetic fields and risk of non-Hodgkin lymphoma

Objectives

To investigate the risk of non‐Hodgkin lymphoma (NHL) using a job‐exposure matrix (JEM) to assess exposure to occupational magnetic fields at the power frequencies of 50/60 Hz.

Methods

The study population consisted of 694 cases of NHL, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupational history was given by each subject. Exposure to power frequency magnetic fields was estimated using a population‐based JEM which was specifically developed in the United States to assess occupational magnetic field exposure. The cumulative exposure distribution was divided into quartiles and adjusted odds ratios were calculated using the lowest quartile as the referent group.

Results

For the total work history, the odds ratio (OR) for workers in the upper quartile of exposure was 1.48 (95% CI 1.02 to 2.16) compared to the referent (p value for trend was 0.006). When the exposure was lagged by 5 years the OR was 1.59 (95% CI 1.07 to 2.36) (p value for trend was 0.003). Adjusting for other occupational exposures did not significantly alter the results.

Conclusions

These findings provide weak support for the hypothesis that occupational exposure to 50/60 Hz magnetic fields increases the risk of NHL.     

Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study

Objectives

To investigate associations of Parkinson''s disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene‐environment interaction effects that modify risk.

Methods

A case‐control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO‐A, MAO‐B, SOD 2, EPHX,DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders.

Results

There was a modest but significant association between MAO‐A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene‐environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only).

Conclusions

Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene‐environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene‐environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.     

Parental exposure to carcinogens and risk for childhood acute lymphoblastic leukemia, Colombia, 2000-2005

Introduction

The objective of this study was to determine the risk factors for childhood acute lymphoblastic leukemia (ALL) and, in particular, the role of parental occupational exposure to carcinogenic and probably carcinogenic hydrocarbons before the child''s conception.

Methods

For this case-control study, cases were children younger than 15 years who were newly diagnosed with ALL between January 2000 and March 2005 at 1 of 6 Colombian hospitals. An interview with both parents of 170 children (85 cases and 85 individually matched neighborhood controls) gathered information about each child''s exposures and parental demographic and occupational characteristics, medical history, health risk behaviors, and pregnancy and birth history. A job-exposure matrix was used to classify parental exposure to hydrocarbons on the basis of the main industrial activity of each workplace where parents worked before (both parents) or during the index pregnancy (mother only). Conditional odds ratios and 95% confidence intervals were calculated by period of exposure (preconception, pregnancy, and childhood).

Results

The risk of childhood ALL was linked to 1) parental occupational exposure to hydrocarbons before conception, 2) parental smoking before conception, 3) maternal low socioeconomic status during pregnancy, and 4) higher maternal age (≥35 y) at the child''s birth.

Conclusion

These findings suggest an association between childhood ALL and parental occupational exposure to carcinogenic and probably carcinogenic hydrocarbons before conception. Outcomes depended on the parent exposed. Future research should investigate the additive or multiplicative role of other environmental sources of hydrocarbons.     

Black Carbon Exposure,Oxidative Stress Genes,and Blood Pressure in a Repeated-Measures Study

Background

Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects.

Objectives

We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM_2.5)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense.

Methods

We performed a repeated-measures analysis in elderly men to analyze associations between PM_2.5 and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1.

Results

A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1–2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2–1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM_2.5 and BP.

Conclusions

We observed positive associations between BP and BC, but not between BP and PM_2.5, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.     

Ambient PM2.5 exposure up-regulates the expression of costimulatory receptors on circulating monocytes in diabetic individuals

Background

Exposure of humans to air pollutants such as ozone and particulate matter (PM) may result in airway and systemic inflammation and altered immune function. One putative mechanism may be through modification of cell-surface costimulatory molecules.

Objectives

We examined whether changes in expression of costimulatory molecules on circulating cells are associated with ambient levels of fine PM [aerodynamic diameter ≤ 2.5 μm (PM_2.5)] in a susceptible population of diabetic individuals.

Methods

Twenty subjects were studied for 4 consecutive days. Daily measurements of PM_2.5 and meteorologic data were acquired on the rooftop of the exam site. Circulating cell-surface markers that mediate innate immune and inflammatory responses were assessed by flow cytometry on each day. Sensitivity analysis was conducted on glutathione S-transferase M1 (GSTM1) genotype, body mass index, and glycosylated hemoglobin A1c (HbA1c) levels to determine their role as effect modifiers. Data were analyzed using random effects models adjusting for season, weekday, and meteorology.

Results

We found significantly increased monocyte expression (mean fluorescent intensity) of CD80, CD40, CD86, HLA-DR, and CD23 per 10-μg/m³ increase in PM_2.5 at 2- to 4-day lag times after exposure. These findings were significantly higher in obese individuals, in individuals with HbA1c > 7%, and in participants who were GSTM1 null.

Conclusions

Exposure to PM_2.5 can enhance antigen-presenting cell phenotypes on circulating cells, which may have consequences in the development of allergic or autoimmune diseases. These effects are amplified in diabetic individuals with characteristics that are associated with insulin resistance or with oxidative stress.     

Traffic-Related Air Pollution and QT Interval: Modification by Diabetes,Obesity, and Oxidative Stress Gene Polymorphisms in the Normative Aging Study

Background

Acute exposure to ambient air pollution has been associated with acute changes in cardiac outcomes, often within hours of exposure.

Objectives

We examined the effects of air pollutants on heart-rate–corrected QT interval (QTc), an electrocardiographic marker of ventricular repolarization, and whether these associations were modified by participant characteristics and genetic polymorphisms related to oxidative stress.

Methods

We studied repeated measurements of QTc on 580 men from the Veterans Affairs Normative Aging Study (NAS) using mixed-effects models with random intercepts. We fitted a quadratic constrained distributed lag model to estimate the cumulative effect on QTc of ambient air pollutants including fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5), ozone (O₃), black carbon (BC), nitrogen dioxide (NO₂), carbon monoxide (CO), and sulfur dioxide (SO₂) concentrations during the 10 hr before the visit. We genotyped polymorphisms related to oxidative stress and analyzed pollution–susceptibility score interactions using the genetic susceptibility score (GSS) method.

Results

Ambient traffic pollutant concentrations were related to longer QTc. An interquartile range (IQR) change in BC cumulative during the 10 hr before the visit was associated with increased QTc [1.89 msec change; 95% confidence interval (CI), −0.16 to 3.93]. We found a similar association with QTc for an IQR change in 1-hr BC that occurred 4 hr before the visit (2.54 msec change; 95% CI, 0.28–4.80). We found increased QTc for IQR changes in NO₂ and CO, but the change was statistically insignificant. In contrast, we found no association between QTc and PM_2.5, SO₂, and O₃. The association between QTc and BC was stronger among participants who were obese, who had diabetes, who were nonsmokers, or who had higher GSSs.

Conclusions

Traffic-related pollutants may increase QTc among persons with diabetes, persons who are obese, and nonsmoking elderly individuals; the number of genetic variants related to oxidative stress increases this effect.     

Brain tumours and exposure to pesticides: a case-control study in southwestern France

Background

Brain tumours are often disabling and rapidly lethal; their aetiology is largely unknown. Among potential risk factors, pesticides are suspected.

Objective

To examine the relationship between exposure to pesticides and brain tumours in adults in a population‐based case–control study in southwestern France.

Methods

Between May 1999 and April 2001, 221 incident cases of brain tumours and 442 individually matched controls selected from the general population were enrolled. Histories of occupational and environmental exposures, medical and lifestyle information were collected. A cumulative index of occupational exposure to pesticides was created, based on expert review of lifelong jobs and tasks. Separate analyses were performed for gliomas and meningiomas.

Results

A non‐statistically significant increase in risk was found for brain tumours when all types of occupational exposure to pesticides were considered (OR = 1.29, 95% CI 0.87 to 1.91) and slightly higher but still non‐statistically significant when gliomas were considered separately (OR = 1.47, 95% CI 0.81 to 2.66). In the highest quartile of the cumulative index, a significant association was found for brain tumours (OR = 2.16, 95% CI 1.10 to 4.23) and for gliomas (OR = 3.21, 95% CI 1.13 to 9.11), but not for meningiomas. A significant increase in risk was also seen for the treatment of home plants (OR = 2.24, 95% CI 1.16 to 4.30) owing to environmental exposure to pesticides.

Conclusions

These data suggest that a high level of occupational exposure to pesticides might be associated with an excess risk of brain tumours, and especially of gliomas.     

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

Background

Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk.

Materials

Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions.

Results

PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures.

Discussion

Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.

Conclusion

Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.     

Associations between temporary employment and occupational injury: what are the mechanisms?

Objective

To determine whether observed higher risks of occupational injury among temporary workers are due to exposure to hazardous working conditions and/or to lack of job experience level.

Methods

Data systematically recorded for 2000 and 2001 by the Spanish Ministry of Labour and Social Affairs on fatal and non‐fatal traumatic occupational injuries were examined by type of employment and type of accident, while adjusting for gender, age, occupation, and length of employment in the company. In the study period there were 1500 fatal and 1 806 532 non‐fatal traumatic occupational injuries that occurred at the workplace. Incidence rates and rate ratios (RR) were estimated using Poisson regression models.

Results

Temporary workers showed a rate ratio of 2.94 for non‐fatal occupational injuries (95% CI 2.40 to 3.61) and 2.54 for fatal occupational injuries (95% CI 1.88 to 3.42). When these associations were adjusted by gender, age, occupation, and especially length of employment, they loose statistic significance: 1.05 (95% CI 0.97 to 1.12) for non‐fatal and 1.07 (95% CI 0.91 to 1.26) for fatal.

Conclusions

Lower job experience and knowledge of workplace hazards, measured by length of employment, is a possible mechanism to explain the consistent association between temporary workers and occupational injury. The role of working conditions associated with temporary jobs should be assessed more specifically.     

Case report: peritoneal mesothelioma from asbestos in hairdryers

Background:

The relationship between mesothelioma and exposure to asbestos is well established. As a result, the use of asbestos in buildings, construction sites, and mines, as well as the implications of disease for the workers has received considerable attention. However, asbestos was also used in household equipment and consumer products, including hairdryers.

Purpose:

To examine one case of peritoneal mesothelioma in a hairdresser and review the relevant literature on asbestos exposure from hairdryers.

Methods:

The subject’s medical and occupational records were obtained and reviewed and a physical examination was performed.

Results:

The results indicate that the subject developed peritoneal mesothelioma from her occupational exposure to asbestos containing hairdryers in accordance with the literature.

Conclusion:

Hairdryers are possible sources of asbestos exposure in patients with mesothelioma, and the asbestos exposure risk is higher for those who use hairdryers occupationally.     

More evidence of unpublished industry studies of lead smelter/refinery workers

Background

Lead smelter/refinery workers in the US have had significant exposure to lead and are an important occupational group to study to understand the health effects of chronic lead exposure in adults. Recent research found evidence that studies of lead smelter/refinery workers have been conducted but not published. This paper presents further evidence for this contention.

Objectives

To present further evidence of industry conducted, unpublished epidemiologic studies of lead smelter/refinery workers and health outcomes.

Methods

Historical research relying on primary sources such as internal industry documents and published studies.

Results

ASARCO smelter/refinery workers were studied in the early 1980s and found to have increased risk of lung cancer and stroke in one study, but not in another.

Conclusions

Because occupational lead exposure is an on-going concern for US and overseas workers, all epidemiologic studies should be made available to evaluate and update occupational health and safety standards.     

Rotenone, paraquat, and Parkinson's disease

Background

Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.

Objectives

Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.

Methods

We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.

Results

In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).

Conclusions

PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.     

Occupational risk factors for nasopharyngeal cancer among female textile workers in Shanghai, China

Aims

To investigate whether occupational exposure to dusts and chemicals in the Chinese textile industry are associated with risk of nasopharyngeal cancer.

Methods

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.

Results

Risk of NPC is associated with cumulative exposure to cotton dust. The hazard ratio for women cumulatively exposed to >143.4 mg/m³ × 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).

Conclusions

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.     

Risk for leukaemia and brain and breast cancer among Danish utility workers: a second follow-up

Objective

To update a study of risks for leukaemia, brain cancer and breast cancer in a Danish nationwide, population‐based cohort of utility employees.

Methods

A multivariate statistical model including information on age, duration of employment, date of first employment and level of occupational exposure to electromagnetic fields was applied.

Results

No increased risk for these cancers was seen among 28 224 subjects with more than 3 months of employment in whom cancer had not been diagnosed before first employment.

Conclusion

The results do not support the hypothesis of an association between occupational exposure to magnetic fields in the electric utility industry and risks for leukaemia, brain cancer and breast cancer.     

Influence of Glutathione S-Transferase Polymorphisms on Cognitive Functioning Effects Induced by p,p′-DDT among Preschoolers

Background

Early-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.

Methods

We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children’s Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.

Results

p,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.

Conclusions

Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.     

A case-control study of occupational exposure to trichloroethylene and non-Hodgkin lymphoma

Background

Previous epidemiologic findings suggest an association between exposure to trichloroethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL).

Objectives

We investigated the association between occupational TCE exposure and NHL within a population-based case–control study using detailed exposure assessment methods.

Methods

Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group.

Results

We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1–6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0–5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose–response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0–4.7).

Conclusions

Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated.     

A Case–Control Study of Lung Cancer Nested in a Cohort of European Asphalt Workers

Background

We conducted a nested case–control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed.

Objective

We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers.

Methods

Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002–2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar.

Results

A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84–1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88–1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate.

Conclusions

We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.