notch1, hif1a and other cancer-related proteins in lung tissue from uranium miners—variation by occupational exposure and subtype of lung cancernotch1 hif1a和其他癌症相关的蛋白在肺组织从铀miners-variation职业暴露和肺癌亚型.pdfVIP

NOTCH1, HIF1A and Other Cancer-Related Proteins in Lung Tissue from Uranium Miners—Variation by Occupational Exposure and Subtype of Lung Cancer 1 1 2 2 1 1 Beate Pesch *, Swaantje Casjens , Ingo Stricker , Daniela Westerwick , Dirk Taeger , Sylvia Rabstein , 1 2 ¨ 1 1 Thorsten Wiethege , Andrea Tannapfel , Thomas Bruning , Georg Johnen 1 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany, 2 Institute of Pathology, Ruhr University Bochum, Bochum, Germany Abstract Background: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. Methodology/Principal Findings: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa), squamous cell carcinoma (SqCC), small cell lung cancer (SCLC), and cancer-free tissue. Within each stratum, we additionally stratified by low or high level of exposure to radon or arsenic. Lifetime exposure to radon and arsenic was estimated using a quantitative job-exposure matrix developed for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and percentage of stained cells. We explored the associations of these scores with cumulative exposure to radon and arsenic with Spearman rank correlation coefficients (rs). Occupational ex