BackgroundAn estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1), ...based on sufficient evidence of lung cancer from epidemiological studies.ObjectiveTo conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking.MethodsThe literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers’s test and Begg’s test.ResultsForty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For ‘ever’ compared with ‘never’ being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I2=26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I2=44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I2=41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I2=6.3%; 15 studies) among ‘shipyard welders’, 1.44 (95% CI 1.07 to 1.95; I2=35.8%; 3 studies) for ‘mild steel welders’ and 1.38 (95% CI 0.89 to 2.13; I2=68.1%; 5 studies) among ‘stainless steel welders’. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype.ConclusionsThese results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking.
Introduction: Responsibility analysis allows the evaluation of crash risk factors from crash data only, but requires a reliable responsibility assessment. The aim of the present study is to predict ...expert responsibility attribution (considered as a gold-standard) from explanatory variables available in crash data routinely recorded by the police, according to a data-driven process with explicit rules. Method: Driver responsibility was assessed by experts using all information contained in police reports for a sample of about 5000 injury crashes that occurred in France in 2011. Three statistical methods were used to predict expert responsibility attribution: logistic regression with L1 penalty, random forests, and boosting. Potential predictors of expert attribution referred to inappropriate driver actions and to external conditions at the time of the crash. Logistic regression was chosen to construct a score to assess responsibility for drivers and riders in crashes involving one or more motor vehicles, or involving a cyclist or pedestrian. Results: Cross-validation showed that our tool can predict expert responsibility assessments on new data sets. In addition, responsibility analyses performed using either the expert responsibility or our predicted responsibility return similar odds ratios. Our scoring process can then be used to reliably assess responsibility based on national police report databases, provided that they include the information needed to construct the score.
•Responsibility assessment quality is essential for valid responsibility analyses.•We developed a data-driven scoring tool to predict responsibility.•In our training set, responsibility of crash-involved drivers was rated by experts.•Predictors mainly referred to inappropriate driver actions.•Cross-validation showed that the scoring tool can be applied on new crash datasets.
The impact of aircraft noise on health is of growing concern. We investigated the relationship between this exposure and mortality from cardiovascular disease, coronary heart disease, myocardial ...infarction, and stroke. We performed an ecological study on 161 communes (commune being the smallest administrative unit in France) close to the following three major French airports: Paris-Charles de Gaulle, Lyon Saint-Exupéry, and Toulouse-Blagnac. The mortality data were provided by the French Center on Medical Causes of Death for the period 2007-2010. Based on the data provided by the French Civil Aviation Authority, a weighted average exposure to aircraft noise (L den AEI) was computed at the commune level. A Poisson regression model with commune-specific random intercepts, adjusted for potential confounding factors including air pollution, was used to investigate the association between mortality rates and L den AEI. Positive associations were observed between L den AEI and mortality from cardiovascular disease adjusted mortality rate ratio (MRR) per 10 dB(A) increase in L den AEI = 1.18; 95% confidence interval (CI): 1.11-1.25, coronary heart disease MRR = 1.24 (1.12-1.36), and myocardial infarction MRR = 1.28 (1.11-1.46. Stroke mortality was more weakly associated with L den AEI MRR = 1.08 (0.97-1.21. These significant associations were not attenuated after the adjustment for air pollution. The present ecological study supports the hypothesis of an association between aircraft noise exposure and mortality from cardiovascular disease, coronary heart disease, and myocardial infarction. However, the potential for ecological bias and the possibility that this association could be due to residual confounding cannot be excluded.
: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin ...B1 from the maternal diet, as measured using biomarkers in the mothers' blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia.
: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (
= 244), in relation to the child's dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months.
: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways.
: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter ...hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited.
We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours.
We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort.
We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.
Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal ...occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case-control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.
In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular ...features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.
Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.
The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.
These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to ...pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development.
We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression.
Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype.
Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings ...offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease.
Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case-control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS).
We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case-control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease.
Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention.
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