Surfactant protein B gene variations and susceptibility to lung cancer in chromate workers.
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AuthorsEwis, Ashraf A.
MetadataShow full item record
AbstractBACKGROUND: Hexavalent chromium has been extensively investigated regarding its mutagenicity and carcinogenicity; however, its mechanism for initiating and enhancing the development of lung cancer is still obscure. Biomarkers of exposure, effect or susceptibility are required for risk assessment and for epidemiologic research studies especially in occupational settings. Since the surfactant protein system (SP) is very important for normal lung function and for mediating local airway conditions and in the clearance of the upper respiratory tract from the occupational and environmental dusts, we hypothesize that SP genes may represent good candidates to study susceptibility for lung cancer. METHODS: Using PCR genotyping methods with gel electrophoresis and confirmation of results with precise DNA fragment size measurement on microchip electrophoresis, we analyzed SP-B intron-4 polymorphism in 230 subjects who were classified into groups; chromate-related lung cancer, control chromate workers who had not developed lung cancer, control individuals with non chromate-related adenocarcinoma or squamous cell carcinoma of the lungs, or healthy Japanese control individuals. RESULTS: Our results indicated that the SP-B variants (deletion/insertion) were significantly overrepresented (61.3%) in the chromate-related lung cancer group than other groups (X2 = 47.6; DF = 4, P = 0.0001). There was a significant difference between the chromate lung cancer group and both of the control groups, healthy individuals and chromate workers who did not develop lung cancer, showing odds ratios (OR) with 95% confidence intervals (CI) of 21.9 (7.3-65.7) and 19.0 (3.78-95.4), respectively. Compared with 46 non chromate-related SCC of the lung, the SP-B variants were significantly overrepresented in the chromate-related SCC (18/28; 64.3%) than the non-chromate SCC (11/46; 23.9%) of the lung samples (X(2) = 10.27, P = 0.01), OR with 95% CI is 5.73 (2.05-16.01). CONCLUSION: These findings indicate a very strong association of the SP-B intron-4 variants with mechanisms that may enhance lung cancer susceptibility, especially in workers who are employed in chromate industry. Moreover, confirmation of such results may help to suggest adding the SP-B intron-4 typing to be one of the screening tests of the pre-placement medical examination to confirm that the worker has no variations of the SP-B gene before being engaged in a chromium-related industry, with the intention of providing proper medical counseling.
CitationAm. J. Ind. Med. 2006, 49 (5):367-373
DescriptionBiomarkers of exposure & early effects: field studiesBiomarker:SP genesExposure/effect represented:chromiumStudy design:case-control studyStudy size:230 japanese individualsAnalytical technique:nested PCR, microchip electroforesis technologyTissue/biological material/sample size:31 lung caner samples, sputum samples for DNA extraction, 89 lymphocyte-DNA extracted samplesImpact on outcome (including dose-response): SP-B gene variants (deletion/insertion) were significantly overrepresented 19/ 31 (61.3%) in the chromate-related lung cancer group of patientsBiomarkers of individual susceptibility: field studiesBiomarker (including alleles if genetic): SP-B intron 4 variantsEffect studied (phenotype/pathology):increased risk for lung cancerTissue/biological material/sample size:31 lung caner samples, sputum samples for DNA extraction, 89 lymphocyte-DNA extracted samplesMethod of analysis:nested PCR, microchip electroforesis technology Study design: case-control studyStudy size: 230 Japanese individualsImpact on outcome (including dose-response):OR= 21.9(7.3-65.7) in the chromate-related lung cancer group and OR=19(3.78-95.4) in the control groups with CI=95%Quality control:38 with adenocarcinoma and 46 samples of squamous cell carcinoma that never participating in the chromate processingNotes:SP-B variants enhance susceptibility of SCC in chromium-related workers. Keywords - classification: adverse effects;biomarkers of individual susceptibility: field studies;chemically induced;Carcinogens;Carcinogens,Environmental;Case-Control Studies;Chromium;Confidence Intervals;genetics;Genetic Predisposition to Disease;Genotype;Humans;Japan;Lung Neoplasms;methods;Metallurgy;Middle Aged;Occupational Diseases;Occupational Exposure;Polymerase Chain Reaction;Protein Precursors;Proteolipids;field studies;genetic;analysis;lymphocytes;