Protein-altering germline mutations implicate novel genes related to lung cancer development.

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.

Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study.

Outdoor particulate matter (PM10) exposure and lung cancer risk in the EAGLE study.

Objective: Cohort studies in Europe, but not in North-America, showed an association between exposure to outdoor particulate matter with aerodynamic diameter ≤10 μm (PM10) and lung cancer risk. Only a case-control study on lung cancer and PM10 in South Korea has so far been performed. For the first time in Europe we analyzed quantitatively this association using a case-control study design in highly polluted areas in Italy.

Effects of aircraft noise on annoyance, sleep disorders, and blood pressure among adult residents near the Orio al Serio International Airport (BGY), Italy.

Background: Aircraft noise may cause several non-auditory health effects, including annoyance, sleep disorders, hypertension, cardiovascular diseases, and impaired cognitive skills in children.

Objectives: To perform a cross-sectional study among adult residents near the Orio al Serio International Airport (BGY), Italy to investigate the association between aircraft noise, annoyance, sleep disorders, blood pressure levels, and prevalence of hypertension.

Methods: Residential addresses of subjects aged 45-70 years were geocoded and classified in three groups according to noise levels: <60 (Reference), 60-65 (Zone A), and 65-75 dBA (Zone B).

Acute particulate matter affects cardiovascular autonomic modulation and IFN-γ methylation in healthy volunteers.

Aims: Air particulate matter (PM) is associated with increased cardiovascular morbidity and mortality. Altered autonomic functions play a key role in PM-induced cardiovascular disease. However, previous studies have not address the impact of PM on sympathetic and parasympathetic control of heart function, independently, and using controlled conditions, i.

Health significance and statistical uncertainty. The value of P-value.

Background: The P-value is widely used as a summary statistics of scientific results. Unfortunately, there is a widespread tendency to dichotomize its value in "P<0.05" (defined as "statistically significant") and "P>0.

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population.

Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation.

Background: Exposure to particulate matter (PM) is associated with increased incidence of cardiovascular disease and increased coagulation, but the molecular mechanisms underlying these associations remain unknown. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects on cardiovascular diseases. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues, might play an important role in PM-induced cardiovascular risk.

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci.

Temporal trends of PM and its impact on mortality in Lombardy, Italy.

Introduction: Exposure to particulate matter with diameter ≤10 μm (PM) entails well documented adverse effects on human health. In the last decade, concentration of PM in Lombardy (10 million inhabitants), Italy, has been gradually decreasing. We evaluated how the mortality burden due to PM varied in that same period.

Assessing the short term impact of air pollution on mortality: a matching approach.

Background: The opportunity to assess short term impact of air pollution relies on the causal interpretation of the exposure-response association. However, up to now few studies explicitly faced this issue within a causal inference framework. In this paper, we reformulated the problem of assessing the short term impact of air pollution on health using the potential outcome approach to causal inference.

Nut Consumption and Lung Cancer Risk: Results from Two Large Observational Studies.

Epidemiologic evidence on the association between nut consumption and lung cancer risk is limited. We investigated this relationship in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, a population-based case-control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2,098 lung cases for EAGLE and 18,533 incident cases in AARP.

A comparative assessment of major international disasters: the need for exposure assessment, systematic emergency preparedness, and lifetime health care.

Background: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members.

Methods: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities.

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study.

Background: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression.

Methods And Findings: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study.

Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study.

Background: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications.

[National survey on workplace safety and prevention services: regional differences].

Background: Occupational Safety and Health (OSH) Services, with inspections and support activities to workers and to enterprises, have a relevant role in the field of safety and health in the workplace.

Objectives: The aim of this study, part of the INSuLa Project, is to realize a national survey about risk perception of OSH and awareness about OSH issues in the context of the Italian OSH legislative framework (Legislative Decree 81/08 and subsequent modifications and integrations) implementation, with involvement of the OSH Services operators.

Methods: The Survey involved a representative national sample of the OSH Services operators.

Incidence of mesothelioma in Lombardy, Italy: exposure to asbestos, time patterns and future projections.

Objectives: In Italy, asbestos has been extensively used from 1945 to 1992. We evaluated the impact of exposure to asbestos on occurrence of malignant mesothelioma (MM) in the Lombardy Region, Northwest Italy, the most populated and industrialised Italian region.

Methods: From the Lombardy Mesothelioma Registry, we selected all incident cases of MM diagnosed between 2000 and 2012.

Geostatistical integration and uncertainty in pollutant concentration surface under preferential sampling.

In this paper the focus is on environmental statistics, with the aim of estimating the concentration surface and related uncertainty of an air pollutant. We used air quality data recorded by a network of monitoring stations within a Bayesian framework to overcome difficulties in accounting for prediction uncertainty and to integrate information provided by deterministic models based on emissions meteorology and chemico-physical characteristics of the atmosphere. Several authors have proposed such integration, but all the proposed approaches rely on representativeness and completeness of existing air pollution monitoring networks.

Determinants of active and environmental exposure to tobacco smoke and upper reference value of urinary cotinine in not exposed individuals.

The aims of this study were (1) to explore the behavioral and sociodemographic factors influencing urinary cotinine (COT-U) levels in active smokers and in environmental tobacco smoke (ETS)-exposed individuals, (2) to assess the specificity and sensitivity of the questionnaire for identifying active smokers and nonsmokers, and (3) to derive the upper reference value of COT-U in non-ETS exposed individuals. The COT-U levels of 495 adults (age range 18-69 years) who classified themselves as active smokers (29%) or as nonsmokers with (17%) or without (83%) ETS exposure were quantified by LC-MS-MS (quantification limit: 0.1µg/L, range of linearity: 0.

Fibrin clot structure is affected by levels of particulate air pollution exposure in patients with venous thrombosis.

Background: Particulate air pollution is a risk factor for cardiovascular diseases and thrombosis. Long-term exposure to particulate matter with a diameter<10μm (PM10) has been associated with an increased risk of venous thrombosis.

Objectives: The aim of this study was to investigate whether or not particulate air pollution alters fibrin clot structure and thus modulates thrombosis risk.

Inflammatory Markers and Genetic Polymorphisms in Workers Exposed to Flour Dust.

Objective: The aim of this study is to evaluate inflammatory markers and pro-inflammatory CD14 and Toll-like Receptor 4 (TLR4) polymorphisms in workers exposed to flour dust.

Methods: Polymorphisms in TLR4 and CD14 were identified in our study population of 167 workers that included 63 healthy subjects (HS), 45 atopic subjects (A), and 59 subjects diagnosed clinically with occupational asthma/rhinitis (OAR). Endpoint measures in this study included fractional exhaled nitric oxide and serum concentrations of interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α).

Air pollution exposure, cause-specific deaths and hospitalizations in a highly polluted Italian region.

Background: The Lombardy region in northern Italy ranks among the most air polluted areas of Europe. Previous studies showed air pollution short-term effects on all-cause mortality. We examine here the effects of particulate matter with aerodynamic diameter ≤10µm (PM10) and nitrogen dioxide (NO2) exposure on deaths and hospitalizations from specific causes, including cardiac, cerebrovascular and respiratory diseases.