Each year over 2,000 new cases of mesothelioma are diagnosed. Mesothelioma is a deadly form of cancer that results from inhaling asbestos dust and particles. There has been some groundbreaking research done regarding risk modifiers and their relationship to mesothelioma. One study on this topic is called, Inherited GSTM1 and NAT2 Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma by Ari Hirvonen, Katarina Pelin, Lauri Tammilehto, Antti Karjalainen, Karin Mattson and Kaija Linnainmaa - Departments of Industria Hygiene and Toxicology [A. H., K. P., K. L.], Epidemiology and Biostatistics [L. T.], and Uusimaa Regional Institute [A. K.], Finnish Institute of Occupational Health, FIN-00250 Helsinki, Finland, and Department of Internal Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland [K. M.] Published in Cancer Research 55, 2981-2983, July 15, 1995. Here is an excerpt:
Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.03.5 and OR = 2.1, 95% CI = 1.14.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.05.6 and OR = 3.7, 95% CI = 1.310.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesot helioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.39.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.634.0).
Another interesting study is called, Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells by Y M Janssen, A Barchowsky, M Treadwell, K E Driscoll, and B T Mossman. Here is an excerpt: Abstract - Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a lucifera se reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.
If you found either of these excerpts helpful, please read the studies in their entirety.
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