Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

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

Fingerprint

Tobacco Products
Chromosome Aberrations
Chromosome Breakage
Lung Neoplasms
Heterochromatin
Glutathione Transferase
Genes
Chromosomes, Human, Pair 1
Genetic Predisposition to Disease
Fluorescence In Situ Hybridization
Population
Carcinogenesis
Biomarkers
Smoking
Lung

Keywords

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

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers. / Conforti-Froes, Nivea; El-Zein, Randa; Abdel-Rahman, Sherif; Zwischenberger, Joseph B.; Au, William W.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 379, No. 1, 05.09.1997, p. 53-59.

Research output: Contribution to journalArticle

Conforti-Froes, Nivea ; El-Zein, Randa ; Abdel-Rahman, Sherif ; Zwischenberger, Joseph B. ; Au, William W. / Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 1997 ; Vol. 379, No. 1. pp. 53-59.
@article{78d57f2857d749b5a5fa0154be2a6e9e,
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) 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.",
keywords = "Chromosome aberration, Cigarette smoker, Lung cancer, Polymorphic GST gene",
author = "Nivea Conforti-Froes and Randa El-Zein and Sherif Abdel-Rahman and Zwischenberger, {Joseph B.} and Au, {William W.}",
year = "1997",
month = "9",
day = "5",
doi = "10.1016/S0027-5107(97)00106-1",
language = "English (US)",
volume = "379",
pages = "53--59",
journal = "Mutation Research",
issn = "0027-5107",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

AU - Conforti-Froes, Nivea

AU - El-Zein, Randa

AU - Abdel-Rahman, Sherif

AU - Zwischenberger, Joseph B.

AU - Au, William W.

PY - 1997/9/5

Y1 - 1997/9/5

N2 - 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.

AB - 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.

KW - Chromosome aberration

KW - Cigarette smoker

KW - Lung cancer

KW - Polymorphic GST gene

UR - http://www.scopus.com/inward/record.url?scp=0030771792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030771792&partnerID=8YFLogxK

U2 - 10.1016/S0027-5107(97)00106-1

DO - 10.1016/S0027-5107(97)00106-1

M3 - Article

C2 - 9330622

AN - SCOPUS:0030771792

VL - 379

SP - 53

EP - 59

JO - Mutation Research

JF - Mutation Research

SN - 0027-5107

IS - 1

ER -