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

doi:10.1016/S0027-5107(97)00106-1

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

Research output: Contribution to journal › Article › peer-review

35 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 language	English
Pages (from-to)	53-59
Number of pages	7
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	379
Issue number	1
DOIs	https://doi.org/10.1016/S0027-5107(97)00106-1
State	Published - Sep 5 1997

Bibliographical note

Funding Information:
This study was supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010), the NIEHS Center (P30 ES 06676) from the US National Institute of Health and a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, to N.C.-F.

Funding

This study was supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010), the NIEHS Center (P30 ES 06676) from the US National Institute of Health and a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, to N.C.-F.

Funders	Funder number
NIEHS Center	P30 ES 06676
National Institutes of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)	P30ES006676
U.S. Environmental Protection Agency	R821003010
Fundação de Amparo à Pesquisa do Estado de São Paulo

Keywords

Chromosome aberration
Cigarette smoker
Lung cancer
Polymorphic GST gene

ASJC Scopus subject areas

Molecular Biology
Genetics
Health, Toxicology and Mutagenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0027-5107(97)00106-1

Cite this

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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 Abdel-Rahman, {Sherif Z.} and Zwischenberger, {Joseph B.} and Au, {William W.}",

note = "Funding Information: This study was supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010), the NIEHS Center (P30 ES 06676) from the US National Institute of Health and a fellowship from Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP), Brazil, to N.C.-F.",

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

AU - Conforti-Froes, Nivea

AU - El-Zein, Randa

AU - Abdel-Rahman, Sherif Z.

AU - Zwischenberger, Joseph B.

AU - Au, William W.

N1 - Funding Information: This study was supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010), the NIEHS Center (P30 ES 06676) from the US National Institute of Health and a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, to N.C.-F.

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

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Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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