Objectives: Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological studies. The authors recently reported updated associations between lung cancer and beryllium exposure in a large, pooled occupational cohort. The authors conducted the present study to evaluate the shape of exposure-response associations between different exposure metrics and lung cancer in this cohort, considering potential confounders (race, plant, professional and short-term work status, and exposure to other lung carcinogens).
Methods: The authors conducted Cox proportional hazards regression analyses of lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA) exposure among 5436 workers, using age-based risk sets. Different exposure-response curves were fitted to the exposure metrics, including categorical, power, restricted cubic spline and piecewise log-linear fits.
Results: The authors found significant positive associations between lung cancer and mean (p < 0.0001) and maximum (p < 0.0001) exposure, adjusting for age, birth cohort and plant, and for cumulative (p = 0.0017) beryllium exposure, adjusting for these factors plus short-term work status and exposure to asbestos. The best-fitting models were generally categorical or piecewise log-linear, with the steepest increase in lung cancer risk between 0 and 10 μg/m(3) for both mean and maximum DWA exposure and between 0 and 200 μg/m(3)-days for cumulative DWA exposure. The estimated mean DWA beryllium exposure associated with 10(-3) excess lifetime risk based on the piecewise log-linear model is 0.033 μg/m(3).
Conclusion: This study provides evidence that lung cancer risk is elevated at levels near the current US Occupational Safety and Health Administration beryllium exposure limit of 2.0 μg/m(3) DWA for workers.
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http://dx.doi.org/10.1136/oem.2010.056515 | DOI Listing |
Ann Surg Oncol
January 2025
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sports Med Open
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Institute of Primary Care, University of Zurich, Zurich, Switzerland.
Background: Marathon training and running have many beneficial effects on human health and physical fitness; however, they also pose risks. To date, no comprehensive review regarding both the benefits and risks of marathon running on different organ systems has been published.
Main Body: The aim of this review was to provide a comprehensive review of the benefits and risks of marathon training and racing on different organ systems.
Nat Commun
January 2025
European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands.
While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.
View Article and Find Full Text PDFCell Death Discov
January 2025
Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory for Information and Decision Systems, Massachusetts Institute of Technology, Cambridge, MA, USA.
Recent barcoding technologies allow reconstructing lineage trees while capturing paired single-cell RNA-sequencing (scRNA-seq) data. Such datasets provide opportunities to compare gene expression memory maintenance through lineage branching and pinpoint critical genes in these processes. Here we develop Permutation, Optimization, and Representation learning based single Cell gene Expression and Lineage ANalysis (PORCELAN) to identify lineage-informative genes or subtrees where lineage and expression are tightly coupled.
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