ABSTRACT
OBJECTIVE: The COVID-19 pandemic underscores the need for workforce awareness-level training for infectious disease outbreaks. A training program was created and evaluated to provide strategies for emergency preparedness as well as worker health and safety during a disease outbreak. METHODS: Participants (N = 292) completed instructor-led synchronous online training modules between January 2022 and February 2023. Training covered 5 areas: vaccine awareness, infectious disease transmission and prevention, pandemic awareness, and inapparent infections, as well as workplace controls to reduce or remove hazards. Participants completed a survey before and after training to assess knowledge change in the five areas. Chi-square analyses assessed how predictors were related to knowledge change. RESULTS: Overall, an increase in knowledge was observed between pre- (80.9%) and post-training (92.7%). Participants from small businesses, with less work experience, and in non-health care roles were under-informed. Knowledge of disease transmission and prevention improved for non-health care professions and workers with less experience. All participants gained knowledge in identifying and ranking safeguards to protect workers from injuries and illness at job sites. CONCLUSIONS: Training improved employee knowledge about safe work practices and pandemic preparedness. Studies should continue to evaluate the effectiveness of preparedness training to prepare the workforce for infectious disease outbreaks and pandemics.
Subject(s)
COVID-19 , Pandemics , Humans , Pandemics/prevention & control , Disease Outbreaks/prevention & control , COVID-19/epidemiology , COVID-19/prevention & control , Surveys and Questionnaires , WorkforceABSTRACT
BACKGROUND: Work is a key social determinant of health. Without the collection of work-related information in public health data systems, the role of social determinants in creating and reinforcing health disparities cannot be fully assessed. METHODS: The Centers for Disease Control and Prevention (CDC) maintains or supports a number of public health surveillance and health monitoring systems, including surveys, case-based disease and exposure systems, vital status records, and administrative data systems. We evaluated a convenience sample of these systems for inclusion of information in three work-related domains: employment status, industry and occupation, and working conditions. RESULTS: While 12 of 39 data systems were identified as collecting work-related data, this information was often minimal (e.g., only employment status), restricted to a subset of respondents, or only gathered periodically. Information on working conditions was particularly sparse. CONCLUSION: Historically, the limited and inconsistent collection of work-related information in public health data systems has hindered understanding of the role work plays in health disparities. Current CDC data modernization efforts present opportunities to enhance the identification and mitigation of health disparities by prioritizing inclusion of an expanded set of work-related data elements.
Subject(s)
Public Health Surveillance , Social Determinants of Health , United States , Humans , Public Health , Centers for Disease Control and Prevention, U.S. , Health InequitiesABSTRACT
The National Institute for Occupational Safety and Health (NIOSH) and several university programs have collaborated on a large effort to expand and improve occupational safety and health content in Wikipedia using a platform developed by Wiki Education. This article describes the initiative, student contributions, and evaluations of this effort by instructors from two universities between 2016 and 2020. The Wiki Education platform allowed instructors to set timelines and track students' progress throughout the semester while students accessed training to best expand health content in Wikipedia. Students chose topics in occupational health based on their interests and by a set of topics deemed as a priority by the "WikiProject Occupational Safety and Health." Students' contributions were peer-reviewed by instructors, NIOSH Wikipedians-in-Residence, and traditional Wikipedians. Students presented their projects in class at the end of the semester. Students from both schools expanded 55 articles, created 8 new articles, and translated 2 articles to Spanish, adding 1270 references; these articles were viewed over 8 million times by May 2020. Feedback received from the implementation suggested that students learned about science communication and digital literacy-providing valuable content on occupational health while reducing misinformation in the public domain. The process of identifying and addressing gaps in occupational health in Wikipedia requires participation and engagement toward improving access to information that otherwise would be restricted to the scientific literature, often behind a paywall. The Wikipedia assignment proved to be an engaging approach for instruction and information literacy. It helped students improve their science communication skills and digital literacy, tools that are likely to be critical for successful communication of science in their future careers.
Subject(s)
Occupational Health , Humans , Students , United StatesABSTRACT
BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk.
Subject(s)
Occupational Exposure , Urinary Bladder Neoplasms , Animals , Humans , Incidence , Occupational Exposure/adverse effects , Risk Assessment , Toluidines , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/epidemiologyABSTRACT
The federally mandated World Trade Center Health Program provides limited health benefits for qualifying health conditions related to the 9/11 terrorist attacks. A qualifying health condition is an illness or health condition for which the member's exposure to airborne toxins, any other hazard, or any other adverse condition resulting from the 9/11 terrorist attacks is considered substantially likely to be a significant factor in aggravating, contributing to, or causing the illness or health condition. These qualifying health conditions are listed in federal regulations. The regulations also provide a process for amending this list. This commentary describes the methods developed for adding health conditions to the list of qualifying health conditions and discusses changes to the list that have occurred during the Program's 2011-2020 period.
Subject(s)
September 11 Terrorist Attacks , Health Promotion , Humans , New York CityABSTRACT
The terrorist attacks on 11 September 2001 potentially exposed more than 400,000 responders, workers, and residents to psychological and physical stressors, and numerous hazardous pollutants. In 2011, the World Trade Center Health Program (WTCHP) was mandated to monitor and treat persons with 9/11-related adverse health conditions and conduct research on physical and mental health conditions related to the attacks. Emerging evidence suggests that persons exposed to 9/11 may be at increased risk of developing mild cognitive impairment. To investigate further, the WTCHP convened a scientific workshop that examined the natural history of cognitive aging and impairment, biomarkers in the pathway of neurodegenerative diseases, the neuropathological changes associated with hazardous exposures, and the evidence of cognitive decline and impairment in the 9/11-exposed population. Invited participants included scientists actively involved in health-effects research of 9/11-exposed persons and other at-risk populations. Attendees shared relevant research results from their respective programs and discussed several options for enhancements to research and surveillance activities, including the development of a multi-institutional collaborative research network. The goal of this report is to outline the meeting's agenda and provide an overview of the presentation materials and group discussion.
Subject(s)
Cognitive Aging , Environmental Pollutants , Mental Disorders , September 11 Terrorist Attacks , Humans , New York CityABSTRACT
Systematic reviews are powerful tools for drawing causal inference for evidence-based decision-making. Published systematic reviews and meta-analyses of environmental and occupational epidemiology studies have increased dramatically in recent years; however, the quality and utility of published reviews are variable. Most methodologies were adapted from clinical epidemiology and have not been adequately modified to evaluate and integrate evidence from observational epidemiology studies assessing environmental and occupational hazards, especially in evaluating the quality of exposure assessments. Although many reviews conduct a systematic and transparent assessment for the potential for bias, they are often deficient in subsequently integrating across a body of evidence. A cohesive review considers the impact of the direction and magnitude of potential biases on the results, systematically evaluates important scientific issues such as study sensitivity and effect modifiers, identifies how different studies complement each other, and assesses other potential sources of heterogeneity. Given these challenges of conducting informative systematic reviews of observational studies, we provide a series of specific recommendations based on practical examples for cohesive evidence integration to reach an overall conclusion on a body of evidence to better support policy making in public health.
Subject(s)
Occupational Health , Causality , Epidemiologic Studies , Humans , Observational Studies as Topic , Public HealthABSTRACT
The terrorist attacks on 11 September 2001 placed nearly a half million people at increased risk of adverse health. Health effects research began shortly after and continues today, now mostly as a coordinated effort under the federally mandated World Trade Center (WTC) Health Program (WTCHP). Established in 2011, the WTCHP provides medical monitoring and treatment of covered health conditions for responders and survivors and maintains a research program aimed to improve the care and well-being of the affected population. By 2020, funds in excess of USD 127 M had been awarded for health effects research. This review describes research findings and provides an overview of the WTCHP and its future directions. The literature was systematically searched for relevant articles published from 11 September 2001 through 30 June 2020. Synthesis was limited to broad categories of mental health, cancer, respiratory disease, vulnerable populations, and emerging conditions. In total, 944 WTC articles were published, including peer-reviewed articles funded by the WTCHP (n = 291) and other sources. Research has focused on characterizing the burden and etiology of WTC-related health conditions. As the program moves forward, translational research that directly enhances the care of individuals with chronic mental and physical health conditions is needed.
Subject(s)
Respiratory Tract Diseases , September 11 Terrorist Attacks , Aged , Child , Health , Humans , Male , New York City , Research , SurvivorsABSTRACT
The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.
Subject(s)
Circadian Rhythm/radiation effects , Lighting , Shift Work Schedule , Sleep/radiation effects , Animals , Electricity , Humans , LightABSTRACT
The exposome has been defined as the totality of exposures individuals experience over the course of their lives and how those exposures affect health. Three domains of the exposome have been identified: internal, specific external, and general external. Internal factors are those that are unique to the individual, and specific external factors include occupational exposures and lifestyle factors. The general external domain includes sociodemographic factors such as educational level and financial status. Eliciting information on the exposome is daunting and not feasible at present; the undertaking may never be fully realized. A variety of tools have been identified to measure the exposome. Biomarker measurements will be one of the major tools in exposomic studies. However, exposure data can also be obtained from other sources such as sensors, geographic information systems, and conventional tools such as survey instruments. Proof-of-concept studies are being conducted that show the promise of exposomic investigation and the integration of different kinds of data. The inherent value of exposomic data in epidemiologic studies is that they can provide greater understanding of the relationships among a broad range of chemical and other risk factors and health conditions and ultimately lead to more effective and efficient disease prevention and control.
Subject(s)
Environmental Exposure/analysis , Epidemiologic Methods , Biochemistry , Biomarkers/analysis , Computational Biology , Genetic Techniques , Geographic Information Systems , HumansABSTRACT
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
Subject(s)
Aging/genetics , Chromosomes, Human, X/genetics , Mosaicism , X Chromosome Inactivation/genetics , DNA Methylation/genetics , Female , Humans , Male , Polymerase Chain Reaction , Reproducibility of ResultsABSTRACT
We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 × 10(-11) ), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with â¼3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma.
Subject(s)
Central Nervous System Neoplasms/genetics , Glioma/genetics , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/genetics , Adenocarcinoma/genetics , Adenocarcinoma of Lung , Adult , Computational Biology , Databases, Nucleic Acid , Genome-Wide Association Study/statistics & numerical data , Glioblastoma/genetics , Humans , Lung Neoplasms/genetics , Middle Aged , RiskABSTRACT
BACKGROUND: Immunoglobulin γ marker (GM) and κ marker (KM) allotypes, hereditary antigenic determinants of γ and κ chains, respectively, have been shown to be associated with immunity to a variety of self and nonself antigens, but their possible contribution to immunity to the tumor-associated antigens epidermal growth factor receptor (EGFR) and EGFR variant (v)III has not been evaluated. The aim of the present investigation was to determine whether the interindividual variation in endogenous antibody responsiveness to EGFR and EGFRvIII is associated with particular GM, KM, and Fcγ receptor (FcγR) genotypes and whether antibody levels were associated with the overall survival of patients with glioblastoma. METHODS: A total of 126 Caucasian participants with glioblastoma were genotyped for several GM, KM, and FcγR alleles and characterized for IgG antibodies to EGFR and EGFRvIII antigens. RESULTS: The anti-EGFR antibody levels associated with GM 3/3 homozygotes and GM 3/17 heterozygotes were similar (15.9 vs 16.4 arbitrary units [AU]/µL) and significantly lower than those associated with GM 17/17 homozygotes (19.6 AU/µL; nominal P = .007). Participants homozygous for the GM 21 allele also had significantly higher levels of anti-EGFR antibodies than GM 5/5 homozygotes and GM 5/21 heterozygotes (20.1 vs 16.0 and 16.3 AU/µL; nominal P = .005). Similar associations were found with immune responsiveness to EGFRvIII. Higher anti-EGFR and anti-EGFRvIII antibody levels were associated with enhanced overall survival (16 vs 11 mo, nominal P = .038 and 20 vs 11 mo, nominal P = .004, respectively). CONCLUSIONS: GM allotypes contribute to humoral immunity to EGFR in glioblastoma.
Subject(s)
ErbB Receptors/immunology , Glioblastoma/genetics , Glioblastoma/immunology , Immunoglobulin Gm Allotypes/genetics , Immunoglobulin Gm Allotypes/immunology , Immunoglobulin Km Allotypes/genetics , Immunoglobulin Km Allotypes/immunology , Adolescent , Adult , Aged , Female , Genotype , Glioblastoma/mortality , Humans , Male , Middle Aged , Receptors, IgG/genetics , Survival , Young AdultABSTRACT
Human cytomegalovirus (HCMV) is a risk factor for many human diseases, but among exposed individuals, not everyone is equally likely to develop HCMV-spurred diseases, implying the presence of host genetic factors that might modulate immunity to this virus. Here, we show that antibody responsiveness to HCMV glycoprotein B (gB) is significantly associated with particular immunoglobulin GM (γ marker) genotypes. Anti-HCMV gB antibody levels were highest in GM 17/17 homozygotes, intermediate in GM 3/17 heterozygotes, and lowest in GM 3/3 homozygotes (28.2, 19.0, and 8.1 µg/mL, respectively; P=.014). These findings provide mechanistic insights in the etiopathogenesis of HCMV-spurred diseases.
Subject(s)
Cytomegalovirus Infections/genetics , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Genes, Immunoglobulin , Immunity, Humoral , Viral Envelope Proteins/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Genotype , Humans , Immunoglobulin Allotypes/genetics , Immunoglobulin Allotypes/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunologyABSTRACT
BACKGROUND: We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006. METHODS: Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o-toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios. RESULTS: Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89-6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non-Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long-term workers exposed to carbon disulfide and shift work for 4 years or more. CONCLUSIONS: Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors.
Subject(s)
Carbon Disulfide/adverse effects , Chemical Industry , Coronary Artery Disease/mortality , Neoplasms/mortality , Occupational Diseases/mortality , Occupational Exposure/statistics & numerical data , Toluidines/adverse effects , Vinyl Chloride/adverse effects , Work Schedule Tolerance , Adult , Aged , Aged, 80 and over , Biliary Tract Neoplasms/mortality , Cohort Studies , Female , Humans , Liver Neoplasms/mortality , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , New York/epidemiology , Risk Factors , Young AdultABSTRACT
BACKGROUND: An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. METHODS: Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. RESULTS: Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. CONCLUSIONS: Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits.
Subject(s)
Chemical Industry , Nitrobenzenes/adverse effects , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Rubber , Toluidines/adverse effects , Urinary Bladder Neoplasms/chemically induced , Adult , Aged , Aged, 80 and over , Aniline Compounds/adverse effects , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , New York/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Proportional Hazards Models , Smoking/adverse effects , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/etiology , Young AdultABSTRACT
BACKGROUND: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. METHODS: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNP). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models. RESULTS: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk. CONCLUSION: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. IMPACT: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma.
Subject(s)
Brain Neoplasms/epidemiology , Brain Neoplasms/genetics , Diabetes Mellitus/epidemiology , Diabetes Mellitus/genetics , Glioma/epidemiology , Glioma/genetics , Aged , Case-Control Studies , China/epidemiology , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Observational Studies as Topic , Polymorphism, Single Nucleotide , Risk Factors , Surveys and Questionnaires , Treatment Outcome , United States/epidemiologyABSTRACT
Understanding the influence someone's job or career has on their health goes beyond the physical, emotional and social hazards, risks and conditions that they face at work. One's job or career also exerts a significant influence over other aspects of life that contribute or detract from their health and that of their family. Work is the major incentive for Latin American migration to the United States. Latino immigrants experience increasingly poorer outcomes for physical health and chronic diseases the longer they remain in the U.S. The strong link between work and immigration suggests that, for many Latin Americans, immigration can be understood as a career path which puts them, and their family members, in situations that can change their physical, emotional, and social health as a condition of their employment. Given the large number of Latin Americans who emigrate for work, it is essential that the unique physical, mental and social impacts of emigration are accounted for when working with clients impacted by emigration at the individual, family and community level as well as those social workers practicing at the system level. This paper is a literature review that explores the impact that emigrating for work has on the health of those that emigrate and their family members that stay behind.
ABSTRACT
Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.
Subject(s)
Brain Neoplasms/genetics , DNA Helicases/genetics , Glioma/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Glioblastoma/genetics , Humans , Male , Middle Aged , Odds Ratio , Sweden , Telomerase/genetics , United StatesABSTRACT
OBJECTIVES: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. RESULTS: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. CONCLUSIONS: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.