Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

Nivea Conforti-Froes, Randa El-Zein, Sherif Z. Abdel-Rahman, Joseph B. Zwischenberger, William W. Au

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34 Scopus citations

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) tandem 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 α-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 influenced 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.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume379
Issue number1
DOIs
StatePublished - Sep 5 1997
Externally publishedYes

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Keywords

  • Chromosome aberration
  • Cigarette smoker
  • Lung cancer
  • Polymorphic GST gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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