Urine proteome profile of firefighters with exposure to emergency fire-induced smoke: A pilot study to identify potential carcinogenic effects.

Firefighters are frequently exposed to a variety of chemicals formed from smoke, which pose a risk for numerous diseases, including cancer. Comparative urine proteome profiling could significantly improve our understanding of the early detection of potential cancer biomarkers. In this study, for the first time, we conducted a comparative protein profile analysis of 20 urine samples collected from ten real-life firefighters prior to and following emergency fire-induced smoke. Using a label-free quantitative proteomics platform, we identified and quantified 1325 unique protein groups, of which 45 proteins showed differential expressions in abundance in response to fire-smoke exposure (post) compared to the control (pre). Pathway analysis showed proteins associated with epithelium development (e.g., RHCG, HEG1, ADAMTSL2) and Alzheimer's disease (SORL1) were significantly increased in response to smoke exposure samples. A protein-protein-network study showed a possible link between these differentially abundant proteins and the known cancer gene (TP53). Moreover, a cross-comparison analysis revealed that seven proteins-ALDH1A1, APCS, POMC, COL2A1, RDX, DDAH2, and SDC4 overlapped with the previously published urine cancer proteome datasets, suggesting a potential cancer risk. Our findings demonstrated that the discovery proteomic platform is a promising analytical technique for identifying potential non-invasive biomarkers associated with fire-smoke exposure in firefighters that may be related to cancer.

Preliminary analyses of accumulation of carcinogenic contaminants on retired firefighter ensembles.

Personal protective equipment (PPE) is designed to protect firefighters from hazards encountered on the fire scene, including heat and products of combustion. Decontamination practices for firefighter turnout gear have been developed to remove combustion products and other contaminants from the fabric of structural firefighting ensembles (i.e., turnout or bunker gear). Chronic exposures to residual polycyclic aromatic hydrocarbons (PAH) are a contributing cause of firefighter cancers. To identify and quantify residual contamination of PAH, samples were taken from two individual decommissioned structural firefighting ensembles and analyzed by layer (outer canvas shell, moisture barrier, and the thermal protective liner) for (1) textile integrity via field emission scanning electron microscopy and (2) quantity of PAH contamination by high-pressure liquid chromatography with ultraviolet/fluorescence detection. The results of these analyses show the presence of the PAH compounds pyrene (35% of the total mass of PAH), phenanthrene (21%), benzo(a)pyrene (14%), and benzo(a)anthracene (14%) which present a risk for dermal absorption. The data also revealed that PAH penetration through the layers of the firefighting ensemble was strongly inhibited by the moisture barrier layer.

Face-to-face with scorching wildfire: potential toxicant exposure and the health risks of smoke for wildland firefighters at the wildland-urban interface.

As wildfire risks have elevated due to climate change, the health risks that toxicants from fire smoke pose to wildland firefighters have been exacerbated. Recently, the International Agency for Research on Cancer (IARC) has reclassified wildland firefighters' occupational exposure as carcinogenic to humans (Group 1). Wildfire smoke contributes to an increased risk of cancer and cardiovascular disease, yet wildland firefighters have inadequate respiratory protection. The economic cost of wildland fires has risen concurrently, as illustrated by the appropriation of $45 billion for wildfire management over FYs 2011-2020 by the U.S. Congress. Occupational epidemiological studies of wildland firefighters are crucial for minimizing health risks; however, they must account for the mixture of exposures in wildfire smoke. This review focuses on four aspects of wildland firefighters' health risks at the wildland-urban interface: 1) economic costs and health impact, 2) respiratory protection, 3) multipollutant mixtures, and 4) proactive management of wildfires.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons in Firefighters: A Systematic Review and Meta-Analysis.

Firefighters are intermittently exposed to complex, mixed pollutants in random settings. Of those pollutants, PAHs (polycyclic aromatic hydrocarbons) are the most commonly studied and best understood. PAH exposure can occur via multiple routes; therefore, the levels of hydroxylated metabolites of PAHs in urine have been used as a biomonitoring tool for risk assessment. We performed a systematic review and meta-analysis of the literature to estimate the levels of urinary hydroxylated PAH (OHPAH) among firefighters, determine risk attributions, and, finally, evaluate the scope of preventive efforts and their utility as diagnostic tools. The meta-regression confirmed increases in OHPAH concentrations after fire activities by up to 1.71-times (p-values: <0.0001). Samples collected at a time point of 2−4 h after a fire suppression showed a consistent, statistically significant pattern as compared with baseline samples. The National Fire Protection Association (NFPA) standard 1582 Standard on Comprehensive Occupational Medical Program for Fire Departments lists various health examinations, including a urinalysis for occupational chemical exposure if indicated and medical screening for cancers and cardiovascular diseases. Biomonitoring is a valuable screening tool for assessing occupational exposure and the results of this meta-analysis support their inclusion in regular health screenings for firefighters.

Validation of a High Flow Rate Puff Topography System Designed for Measurement of Sub-Ohm, Third Generation Electronic Nicotine Delivery Systems.

There are few known puff topography devices designed solely for gathering electronic cigarette puff topography information, and none made for high-powered sub-ohm devices. Ten replicate Bernoulli flow cells were designed and 3D printed. The relationship between square root of pressure difference and flow rate was determined across 0−70 L/min. One representative flow cell was used to estimate puff volume and flow rate under six simulated puffing regimes (0.710 L, 2.000 L and 3.000 L, at low and high flow rates) to determine the system's accuracy and utility of using dual pressure sensors for flow measurement. The relationship between flow rate and square root of pressure differential for the ten replicate cells was best fit with a quadratic model (R2 = 0.9991, p < 0.0001). The higher-pressure sensor was accurate at both low and high flow rates for 0.71 L (102% and 111% respectively), 2.00 L (96% and 103% respectively), and 3.00 L (100.1% and 107% respectively) but the lower-pressure sensor provided no utility, underpredicting volume and flow. This puff topography system generates very little resistance to flow, easily fits between user's atomizer and mouthpiece, and is calibrated to measure flows up to 70 L/min.

Using Collaborative Partnerships to Engage Firefighters in Rural Communities.

The purpose of this study was to utilize community-based participatory research (CBPR) methods to identify behaviors that may increase the exposure rates of firefighters to carcinogens and other occupational hazards. Key informant interviews and focus groups were conducted as part of a larger study that included exposure assessments at fire stations, in fire engines, and in personal vehicles. A purposive sample of five fire chiefs and leaders of the firefighter association was chosen, and these individuals were selected to participate in interviews. Unstructured interviews explored issues related to firefighter exposures and occupational hazards. Three focus groups were conducted over a three-month period. Following the focus groups, survey questions emphasizing the following three aspects of firefighting were developed: exposure to airborne smoke contaminants during fire suppression, accumulated exposure on turnout gear after fire suppression, and exposure to airborne contaminants at the fire departments. The use of community-based participatory research can be very beneficial, especially when conducting research with a group that may be hard to reach or have misgivings regarding researchers. By utilizing this approach in the current study, researchers were able to partner with a community that may be hard to reach and gain buy-in from community leadership.

Asbestos Detection with Fluorescence Microscopy Images and Deep Learning.

Fluorescent probes can be used to detect various types of asbestos (serpentine and amphibole groups); however, the fiber counting using our previously developed software was not accurate for samples with low fiber concentration. Machine learning-based techniques (e.g., deep learning) for image analysis, particularly Convolutional Neural Networks (CNN), have been widely applied to many areas. The objectives of this study were to (1) create a database of a wide-range asbestos concentration (0-50 fibers/liter) fluorescence microscopy (FM) images in the laboratory; and (2) determine the applicability of the state-of-the-art object detection CNN model, YOLOv4, to accurately detect asbestos. We captured the fluorescence microscopy images containing asbestos and labeled the individual asbestos in the images. We trained the YOLOv4 model with the labeled images using one GTX 1660 Ti Graphics Processing Unit (GPU). Our results demonstrated the exceptional capacity of the YOLOv4 model to learn the fluorescent asbestos morphologies. The mean average precision at a threshold of 0.5 (mAP@0.5) was 96.1% ± 0.4%, using the National Institute for Occupational Safety and Health (NIOSH) fiber counting Method 7400 as a reference method. Compared to our previous counting software (Intec/HU), the YOLOv4 achieved higher accuracy (0.997 vs. 0.979), particularly much higher precision (0.898 vs. 0.418), recall (0.898 vs. 0.780) and F-1 score (0.898 vs. 0.544). In addition, the YOLOv4 performed much better for low fiber concentration samples (<15 fibers/liter) compared to Intec/HU. Therefore, the FM method coupled with YOLOv4 is remarkable in detecting asbestos fibers and differentiating them from other non-asbestos particles.

Health Risks of Structural Firefighters from Exposure to Polycyclic Aromatic Hydrocarbons: A Systematic Review and Meta-Analysis.

Firefighters have an elevated risk of cancer, which is suspected to be caused by occupational and environmental exposure to fire smoke. Among many substances from fire smoke contaminants, one potential source of toxic exposure is polycyclic aromatic hydrocarbons (PAH). The goal of this paper is to identify the association between PAH exposure levels and contributing risk factors to derive best estimates of the effects of exposure on structural firefighters' working environment in fire. We surveyed four databases (Embase, Medline, Scopus, and Web of Science) for this systematic literature review. Generic inverse variance method for random effects meta-analysis was applied for two exposure routes-dermal and inhalation. In dermal, the neck showed the highest dermal exposure increased after the fire activity. In inhalation, the meta-regression confirmed statistically significant increases in PAH concentrations for longer durations. We also summarized the scientific knowledge on occupational exposures to PAH in fire suppression activities. More research into uncontrolled emergency fires is needed with regard to newer chemical classes of fire smoke retardant and occupational exposure pathways. Evidence-based PAH exposure assessments are critical for determining exposure-dose relationships in large epidemiological studies of occupational risk factors.

A Bayesian Approach for Determining the Relationship Between Various Elongate Mineral Particles (EMPs) Definitions.

A variety of dimensions (lengths and widths) of elongate mineral particles (EMPs) have been proposed as being related to health effects. In this paper, we develop a mathematical approach for deriving numerical conversion factors (CFs) between these EMP exposure metrics and applied it to the Minnesota Taconite Health Worker study which contains 196 different job exposure groups (28 similar exposure groups times 7 taconite mines). This approach comprises four steps: for each group (i) obtain EMP dimension information using ISO-TEM 10312/13794 analysis; (ii) use bivariate lognormal distribution to characterize overall EMP size distribution; (iii) use a Bayesian approach to facilitate the formation of the bivariate lognormal distribution; (iv) derive conversion factors between any pair of EMP definitions. The final CFs allow the creation of job exposure matrices (JEMs) for alternative EMP metrics using existing EMP exposures already characterized according to the National Institute of Occupational Safety and Health (NIOSH)-defined EMP exposure metric (length >5 µm with an aspect ratio ≥3.0). The relationships between the NIOSH EMP and other EMP definitions provide the basis of classification of workers into JEMs based on alternate definitions of EMP for epidemiological studies of mesothelioma, lung cancer, and non-malignant respiratory disease.

Examining Behaviors Related to Retirement, Cleaning, and Storage of Turnout Gear Among Rural Firefighters.

Background: Although the increased occupational exposures among career firefighters are well documented, there are gaps in research related to exposures among volunteer firefighters. This study was completed in a state where the majority of firefighters are volunteers. We aimed to examine if differences existed in career versus volunteer firefighters' behaviors related to the retirement, cleaning, and storage of turnout gear which may increase occupational exposures. Methods: A cross-sectional survey was administered to a convenience sample of 300 firefighters during a training event for both volunteer and career firefighters from one fire district in Kentucky. We measured factors that may affect behaviors related to retirement, cleaning, and storage of turnout gear, such as age of turnout gear at retirement, frequency of cleaning, and location of storage. Results: Two hundred and seventy-five firefighters out of 300 invited participants completed the survey, for a response rate of 92%. The majority of the participants were compliant with National Fire Protection Association Standards with most reporting cleaning their gear as needed, storing gear at the fire station, and retiring gear within 10 years of the manufactured date. Most of the participants (88%) were concerned about job-related exposures and felt susceptible to diseases like cancer and respiratory illness. The structural issues of cost and accessibility were identified as the primary barriers to the proper retirement and cleaning of turnout gear, especially among volunteer firefighters. Conclusions/Application to Practice: Most participants retired, cleaned, and stored turnout as recommended. The majority of participants were concerned with job-related exposures. The structural issues of cost and accessibility were identified as the primary barriers to the proper retirement and cleaning of turnout gear, especially among volunteer firefighters. By identifying differences, tailored trainings could be aimed at volunteer firefighters to help reduce their exposures.

The Korean undiagnosed diseases program: lessons from a one-year pilot project.

BACKGROUND: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea. RESULTS: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and 59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study, 72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients also underwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved molecular genetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single or targeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, among whom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration. CONCLUSIONS: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic success rate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDP also satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomic technologies for further research into rare and still-undiagnosed conditions.

Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for the risk of type 2 diabetes mellitus.

Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external validation, we replicated the T2D-association at a novel CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D-discordant MZTW. For concordant DNA methylation signatures in tissues, we further confirmed that a CpG site (cg18681426) was associated with adipogenic differentiation between human preadipocytes and adipocytes isolated from the same biopsy sample. In addition, the ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated T2D patients and in human pancreatic islets. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes. These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers.

Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population.

PURPOSE: To investigate exome-wide genetic variants associated with prostate cancer (PCa) in Koreans and evaluate the discriminative ability by the genetic risk score (GRS). PATIENTS AND METHODS: We prospectively recruited 1,001 PCa cases from a tertiary hospital and conducted a case-control study including 2,641 healthy men (Stage I). Participants were analyzed using HumanExome BeadChip. For the external validation, additionally enrolled 514 PCa cases and 548 controls (independent cohort) were analyzed for the identified single nucleotide polymorphisms (SNPs) of Stage I (Stage II). The GRS was calculated as a non-weighted sum of the risk allele counts and investigated for accuracy of prediction of PCa. RESULTS: the mean age was 66.3 years, and the median level of prostate specific antigen (PSA) was 9.19 ng/ml in PCa cases. In Stage I, 4 loci containing 5 variants (rs1512268 on 8p21.2; rs1016343 and rs7837688 on 8q24.21; rs7501939 on 17q12, and rs2735839 on 19q13.33) were confirmed to reach exome-wide significance (p<8.3x10-7). In Stage II, the mean GRS was 4.23 ± 1.44 for the controls and 4.78 ± 1.43 for the cases. As a reference to GRS 4, GRS 6, 7 and 8 showed a statistically significant risk of PCa (OR=1.85, 2.11 and 3.34, respectively). CONCLUSIONS: The five variants were validated to associate with PCa in firstly performed exome-wide study in Koreans. The addition of individualized calculated GRS effectively enhanced the accuracy of prediction. These results need to be validated in future studies.

Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with ß-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. METHODS: Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. RESULTS: ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. CONCLUSIONS: Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. LAY SUMMARY: Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D.

Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.

Fasting plasma glucose (FPG) has been recognized as an important indicator for the overall glycemic state preceding the onset of metabolic diseases. So far, most indentified genome-wide association loci for FPG were derived from populations with European ancestry, with a few exceptions. To extend a thorough catalog for FPG loci, we conducted meta-analyses of 13 genome-wide association studies in up to 24,740 nondiabetic subjects with East Asian ancestry. Follow-up replication analyses in up to an additional 21,345 participants identified three new FPG loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R. Our results could provide additional insight into the genetic variation implicated in fasting glucose regulation.

The relationship between various exposure metrics for elongate mineral particles (EMP) in the taconite mining and processing industry.

Different dimensions of elongate mineral particles (EMP) have been proposed as being relevant to respiratory health end-points such as mesothelioma and lung cancer. In this article, a methodology for converting personal EMP exposures measured using the National Institute for Occupational Safety and Health (NIOSH) 7400/7402 methods to exposures based on other size-based definitions has been proposed and illustrated. Area monitoring for EMP in the taconite mines in Minnesota's Mesabi Iron Range was conducted using a Micro Orifice Uniform Deposit Impactor (MOUDI) size-fractionating sampler. EMP on stages of the MOUDI were counted and sized according to each EMP definition using an indirect-transfer transmission electron microscopy (ISO Method 13794). EMP were identified using energy-dispersive x-ray and electron diffraction analysis. Conversion factors between the EMP counts based on different definitions were estimated using (1) a linear regression model across all locations and (2) a location-specific ratio of the count based on each EMP definition to the NIOSH 7400/7402 count. The highest fractions of EMP concentrations were found for EMP that were 1-3 µm in length and 0.2-0.5 µm in width. Therefore, the current standard NIOSH Method 7400, which only counts EMP >5 µm in length and ≥ 3 in aspect ratio, may underestimate amphibole EMP exposures. At the same time, there was a high degree of correlation between the exposures estimated according to the different size-based metrics. Therefore, the various dimensional definitions probably do not result in different dose-response relationships in epidemiological analyses. Given the high degree of correlation between the various metrics, a result consistent with prior research, a more reasonable metric might be the measurement of all EMP irrespective of size. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: figures detailing EMP concentration.].

Male-specific genetic effect on hypertension and metabolic disorders.

Genetic risk factors for hypertension may have age or gender specificity and pleiotropic effects. This study aims to measure the risk of genetic and non-genetic factors in the occurrence of hypertension and related diseases, with consideration of potential confounding factors and age-gender stratification. A discovery set of 352,228 genotyped plus 1.8 million imputed single-nucleotide polymorphisms were analyzed for 2,886 hypertensive cases and 3,440 healthy controls obtained from two community-based cohorts in Korea, and selected gene variants were replicated in the Health Examinee cohort (665 cases and 1,285 controls). Genome-wide association analyses were conducted in 12 groups stratified by age and gender after adjusting for potential covariates under three genetic models. Age, rural area residence, body mass index, family history of hypertension, male gender, current alcohol drinking status, and current smoking status were significantly associated with hypertension (P = 4 × 10(-151) to 0.011). Five gene variants, rs11066280 (C12orf51), rs12229654 and rs3782889 (MYL2), rs2072134 (OAS3), rs2093395 (TREML2), and rs17249754 (ATP2B1), were found to be associated with hypertension mostly in men (P = 4.76 × 10(-14) to 4.46 × 10(-7) in the joint analysis); three SNPs (rs11066280, rs12229654, and rs3782889) remained significant after Bonferroni correction in an independent population. Three gene variants, rs12229654, rs17249754, and rs11066280, were significantly associated with metabolic disorders such as hyperlipidemia and diabetes (P = 0.00071 to 0.0097, respectively). Careful consideration of the potential confounding effects in future genome-wide association studies is necessary to uncover the genetic underpinnings of complex diseases.

Comprehensive assessment of exposures to elongate mineral particles in the taconite mining industry.

Since the 1970s, concerns have been raised about elevated rates of mesothelioma in the vicinity of the taconite mines in the Mesabi Iron Range. However, insufficient quantitative exposure data have hampered investigations of the relationship between cumulative exposures to elongate mineral particles (EMP) in taconite dust and adverse health effects. Specifically, no research on exposure to taconite dust, which includes EMP, has been conducted since 1990. This article describes a comprehensive assessment of present-day exposures to total and amphibole EMP in the taconite mining industry. Similar exposure groups (SEGs) were established to assess present-day exposure levels and buttress the sparse historical data. Personal samples were collected to assess the present-day levels of worker exposures to EMP at six mines in the Mesabi Iron Range. The samples were analyzed using National Institute for Occupational Safety and Health (NIOSH) methods 7400 and 7402. For many SEGs in several mines, the exposure levels of total EMP were higher than the NIOSH Recommended Exposure Limit (REL). However, the total EMP classification includes not only the asbestiform EMP and their non-asbestiform mineral analogs but also other minerals because the NIOSH 7400 cannot differentiate between these. The concentrations of amphibole EMP were well controlled across all mines and were much lower than the concentrations of total EMP, indicating that amphibole EMP are not major components of taconite EMP. The levels are also well below the NIOSH REL of 0.1 EMP cc(-1). Two different approaches were used to evaluate the variability of exposure between SEGs, between workers, and within workers. The related constructs of contrast and homogeneity were calculated to characterize the SEGs. Contrast, which is a ratio of between-SEG variability to the sum of between-SEG and between-worker variability, provides an overall measure of whether there are distinctions between the SEGs. Homogeneity, which is the ratio of the within-worker variance component to the sum of the between-worker and within-worker variance components, provides an overall measure of how similar exposures are for workers within an SEG. Using these constructs, it was determined that the SEGs are formed well enough when grouped by mine for both total and amphibole EMP to be used for epidemiological analysis.

Recapitulation of previous genome-wide association studies with two distinct pathophysiological entities of gastric cancer in the Korean population.

Gastric cancer (GC) is the most common malignancy. The incidence rates remain remarkably high in East Asians. Although genome-wide association studies in the Han Chinese and Japanese populations have so far yielded susceptibility loci for GC, these findings need to be validated in an independent ethnic group. To identify the potential heterogeneity by histological classified subtypes (intestinal and diffuse), we examined the previously reported associations in the Korean population. PRKAA1 at 5p13.1 was found to be more strongly associated with intestinal type (odds ratio, OR=1.39, 95% CI (confidence interval) =1.22-1.58, P=3.77 × 10(-7)) than diffuse type. In addition, PSCA at 8q23.3 was significantly replicated in diffuse type (OR=1.49, 95% CI=1.32-1.67, P=2.43 × 10(-11)) but far less significant in intestinal type. In conclusion, these findings could bring additional insights into the etiologic heterogeneity in gastric carcinogenesis mechanisms.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.

BACKGROUND: Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. METHODS: Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. RESULTS: In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10(-8); OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. CONCLUSIONS: Our findings provide new insights into the genetic architecture underlying OF in East Asians.