title: Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients.
abstract: The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobacco smoke exposure and occupational asbestos exposure available for the cases. The principal aim of the present study was to investigate whether absent or reduced Fhit expression or FHIT allele loss was associated with exposure to these pulmonary carcinogens. We detected reduced Fhit expression in 62% (33/53) of the cases analysed. Prevalence of allele loss at the FHIT locus was 22% (20/89). Reduced protein expression was common both in the asbestos-exposed (67%) and non-exposed cases (59%); [odds ratio (OR) 1.4, 95% confidence interval (CI) 0.4-4.9]. LOH frequencies differed somewhat between the two groups and were 25% vs. 16%, respectively (OR 1.8; 95% CI 0.5-5.9). Absent or reduced expression was common in smokers, with no significant difference found between current smokers and non-smokers (mainly former smokers) (OR 1.4, 95% CI 0.5-4.5). NSCLCs with squamous cell histology exhibited both aberrant expression (OR 3.1, 95% CI 0.9-10.3) and allele loss (OR 3.3, 95% CI 0.9-12.7) more frequently than adenocarcinoma. Finally, we found that FHIT allele loss was increased in stage II or more advanced disease (OR 2.5, 95% CI 0.9-7.4), and in poorly differentiated tumours (grade 3, OR 2.6, 95% CI 0.8-8.1). In conclusion, our present data support significance of FHIT inactivation in development of lung cancer.
authors.affiliation: Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Lea
authors.initials: L
authors.lastname: Pylkkanen
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Tuula
authors.initials: T
authors.lastname: Stjernvall
authors.forename: Paivi
authors.initials: P
authors.lastname: Tuominen
authors.forename: Thanos
authors.initials: T
authors.lastname: Sioris
authors.forename: Antti
authors.initials: A
authors.lastname: Karjalainen
authors.forename: Sisko
authors.initials: S
authors.lastname: Anttila
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
mesh_terms: D017766:Acid Anhydride Hydrolases; D001194:Asbestos / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D009367:Neoplasm Staging; D012907:Smoking / Q000009:adverse effects*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D001194:Asbestos; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase