title: Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers.
abstract: Genotoxic effects linking cigarette smoking with lung cancer have not been consistently demonstrated, therefore claims for the cause-effect relationships are vigorously contested. Using matched populations of 22 lung cancer patients who have been cigarette smokers (LCP), 22 non-cancerous cigarette smokers (SC) and 13 non-smokers (NSC), we have applied the fluorescence in situ hybridization (FISH) tanden probe assay to elucidate the frequency of chromosome breakage among the participants. Two probes were used, a classical satellite probe which hybridizes to the large heterochromatin region of chromosome 1, and an alpha-satellite probe which targets a small region adjacent to the heterochromatin probe. The highest frequency of structural aberrations was observed in LCP (1.4 +/- 0.1) followed by SC (1.25 +/- 0.1) and NSC (0.4 +/- 0.1). Aberration frequencies were not significantly different between LCP and SC (p > 0.05), however, a statistically significant difference was detected between the smoker populations combined (LCP and SC) and the NSC (p < 0.001). The breakage frequencies showed a positive correlation with duration of smoking for LCP (r = 0.5; p < 0.01), but not for SC (P > 0.05). In addition, the aberration frequencies were influences by the inheritance of polymorphic glutathione S-transferase (GST) genes. LCPs missing one or the other GST (GSTM1 or GSTT1) genes were found to have significantly higher chromosome breaks compared to LCPs with both genes present (p < 0.05). Our data indicate that genetic predisposition and chromosome aberrations may be mechanistically related to the initiation of lung carcinogenesis; therefore, they may be useful biomarkers for lung cancer among cigarette smokers.
authors.affiliation: Instituto de Biociencias, Universidade Estadual Paulista, Sao Jose Do Rio Preto, Brazil.
authors.forename: N
authors.initials: N
authors.lastname: Conforti-Froes
authors.forename: R
authors.initials: R
authors.lastname: el-Zein
authors.forename: S Z
authors.initials: SZ
authors.lastname: Abdel-Rahman
authors.forename: J B
authors.initials: JB
authors.lastname: Zwischenberger
authors.forename: W W
authors.initials: WW
authors.lastname: Au
mesh_terms: D000704:Analysis of Variance; D002869:Chromosome Aberrations / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D005796:Genes; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012907:Smoking / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase