Interactions between genetic predisposition and environmental toxicants for development of lung cancer
Autor(a) principal: | |
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Data de Publicação: | 1997 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/(SICI)1098-2280(1997)30:2<196 http://hdl.handle.net/11449/219200 |
Resumo: | Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (>30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (<30 pack-years) the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% CL = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variatons in cancer outcome, to identify high risk individuals and to assess health risk. |
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Interactions between genetic predisposition and environmental toxicants for development of lung cancerEnvironmental toxicantsLung cancer riskPolymorphic genesSignificant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (>30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (<30 pack-years) the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% CL = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variatons in cancer outcome, to identify high risk individuals and to assess health risk.Depts. Hum. Biol. Chem. and Genet. Prev. Medicine and Community Health University of Texas Medical Branch, Galveston, TXInstituto de Biociencias Universidade Estadual Paulista, Sao Jose do Rio Preto2.102 Ewing Hall Prev. Medicine and Community Health University of Texas Medical Branch, 700 Harborside Drive, Galveston, TX 77555-1110Instituto de Biociencias Universidade Estadual Paulista, Sao Jose do Rio PretoUniversity of Texas Medical BranchUniversidade Estadual Paulista (UNESP)El-Zein, RandaConforti-Froes, Nivea [UNESP]Au, William W.2022-04-28T18:54:22Z2022-04-28T18:54:22Z1997-10-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article196-204http://dx.doi.org/10.1002/(SICI)1098-2280(1997)30:2<196Environmental and Molecular Mutagenesis, v. 30, n. 2, p. 196-204, 1997.0893-6692http://hdl.handle.net/11449/21920010.1002/(SICI)1098-2280(1997)30:2<1962-s2.0-0030850660Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengEnvironmental and Molecular Mutagenesisinfo:eu-repo/semantics/openAccess2022-04-28T18:54:22Zoai:repositorio.unesp.br:11449/219200Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:19:31.588600Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
title |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
spellingShingle |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer El-Zein, Randa Environmental toxicants Lung cancer risk Polymorphic genes |
title_short |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
title_full |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
title_fullStr |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
title_full_unstemmed |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
title_sort |
Interactions between genetic predisposition and environmental toxicants for development of lung cancer |
author |
El-Zein, Randa |
author_facet |
El-Zein, Randa Conforti-Froes, Nivea [UNESP] Au, William W. |
author_role |
author |
author2 |
Conforti-Froes, Nivea [UNESP] Au, William W. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
University of Texas Medical Branch Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
El-Zein, Randa Conforti-Froes, Nivea [UNESP] Au, William W. |
dc.subject.por.fl_str_mv |
Environmental toxicants Lung cancer risk Polymorphic genes |
topic |
Environmental toxicants Lung cancer risk Polymorphic genes |
description |
Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (>30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (<30 pack-years) the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% CL = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variatons in cancer outcome, to identify high risk individuals and to assess health risk. |
publishDate |
1997 |
dc.date.none.fl_str_mv |
1997-10-25 2022-04-28T18:54:22Z 2022-04-28T18:54:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1002/(SICI)1098-2280(1997)30:2<196 Environmental and Molecular Mutagenesis, v. 30, n. 2, p. 196-204, 1997. 0893-6692 http://hdl.handle.net/11449/219200 10.1002/(SICI)1098-2280(1997)30:2<196 2-s2.0-0030850660 |
url |
http://dx.doi.org/10.1002/(SICI)1098-2280(1997)30:2<196 http://hdl.handle.net/11449/219200 |
identifier_str_mv |
Environmental and Molecular Mutagenesis, v. 30, n. 2, p. 196-204, 1997. 0893-6692 10.1002/(SICI)1098-2280(1997)30:2<196 2-s2.0-0030850660 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Environmental and Molecular Mutagenesis |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
196-204 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128347732967424 |