Association between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1
Background: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metab...
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| Veröffentlicht in: | Environmental health perspectives 2009-02, Vol.117 (2), p.203-208 |
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| creator | Rossi, Anna Maria Hansteen, Inger-Lise Skjelbred, Camilla Furu Ballardin, Michela Maggini, Valentina Murgia, Elena Tomei, Antonio Viarengo, Paolo Knudsen, Lisbeth E. Barale, Roberto Norppa, Hannu Bonassi, Stefano |
| description | Background: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. Objectives: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. Methods: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. Results: The association between CA frequency and cancer risk was confirmed [${\rm OR}_{\text{medium}}$
$(\text{odds ratio})_{\text{medium}}=1.5$, 95% credibility interval (CrI), 0.9-2.5;${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (${\rm OR}_{\text{high}}=9.4$, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (${\rm OR}_{\text{high}}=6.2$, 95% CrI, 1.5-20.0), the genitourinary tract (${\rm OR}_{\text{high}}=4.0$, 95% CrI, 1.4-10.0), and the digestive tract (${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.2-5.8). Conclusions: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms. |
| doi_str_mv | 10.1289/ehp.11769 |
| format | Article |
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$(\text{odds ratio})_{\text{medium}}=1.5$, 95% credibility interval (CrI), 0.9-2.5;${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (${\rm OR}_{\text{high}}=9.4$, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (${\rm OR}_{\text{high}}=6.2$, 95% CrI, 1.5-20.0), the genitourinary tract (${\rm OR}_{\text{high}}=4.0$, 95% CrI, 1.4-10.0), and the digestive tract (${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.2-5.8). Conclusions: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.</description><identifier>ISSN: 0091-6765</identifier><identifier>EISSN: 1552-9924</identifier><identifier>DOI: 10.1289/ehp.11769</identifier><identifier>PMID: 19270789</identifier><language>eng</language><publisher>United States: National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</publisher><subject>Aberration ; Adult ; Bayesian analysis ; Biological markers ; Blood ; Cancer ; Case control studies ; Chromosome Aberrations ; Chromosome abnormalities ; Control ; Control equipment ; Copyrights ; Cytogenetics ; DNA ; DNA repair ; Environmental aspects ; Enzymes ; Female ; Genetic aspects ; Genetic polymorphism ; Genetic polymorphisms ; Genetic Predisposition to Disease - genetics ; Genetics ; Genotype ; Genotypes ; Glutathione ; Glutathione transferase ; Glutathione Transferase - genetics ; Health ; Health aspects ; Humans ; Intervals ; Lymphocytes ; Male ; Maria ; Mathematical models ; Middle Aged ; Neoplasms - genetics ; Polymorphism ; Polymorphism, Genetic - genetics ; Risk ; Risk factors ; Tobacco smoking</subject><ispartof>Environmental health perspectives, 2009-02, Vol.117 (2), p.203-208</ispartof><rights>COPYRIGHT 2009 National Institute of Environmental Health Sciences</rights><rights>Copyright National Institute of Environmental Health Sciences Feb 2009</rights><rights>2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5e5d46fda8091e6bd0e718adc4880753e95656c79d8fd81e76f591df2d6471cb3</citedby><cites>FETCH-LOGICAL-c692t-5e5d46fda8091e6bd0e718adc4880753e95656c79d8fd81e76f591df2d6471cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25434926$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25434926$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,860,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19270789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rossi, Anna Maria</creatorcontrib><creatorcontrib>Hansteen, Inger-Lise</creatorcontrib><creatorcontrib>Skjelbred, Camilla Furu</creatorcontrib><creatorcontrib>Ballardin, Michela</creatorcontrib><creatorcontrib>Maggini, Valentina</creatorcontrib><creatorcontrib>Murgia, Elena</creatorcontrib><creatorcontrib>Tomei, Antonio</creatorcontrib><creatorcontrib>Viarengo, Paolo</creatorcontrib><creatorcontrib>Knudsen, Lisbeth E.</creatorcontrib><creatorcontrib>Barale, Roberto</creatorcontrib><creatorcontrib>Norppa, Hannu</creatorcontrib><creatorcontrib>Bonassi, Stefano</creatorcontrib><title>Association between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1</title><title>Environmental health perspectives</title><addtitle>Environ Health Perspect</addtitle><description>Background: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. Objectives: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. Methods: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. Results: The association between CA frequency and cancer risk was confirmed [${\rm OR}_{\text{medium}}$
$(\text{odds ratio})_{\text{medium}}=1.5$, 95% credibility interval (CrI), 0.9-2.5;${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (${\rm OR}_{\text{high}}=9.4$, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (${\rm OR}_{\text{high}}=6.2$, 95% CrI, 1.5-20.0), the genitourinary tract (${\rm OR}_{\text{high}}=4.0$, 95% CrI, 1.4-10.0), and the digestive tract (${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.2-5.8). Conclusions: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.</description><subject>Aberration</subject><subject>Adult</subject><subject>Bayesian analysis</subject><subject>Biological markers</subject><subject>Blood</subject><subject>Cancer</subject><subject>Case control studies</subject><subject>Chromosome Aberrations</subject><subject>Chromosome abnormalities</subject><subject>Control</subject><subject>Control equipment</subject><subject>Copyrights</subject><subject>Cytogenetics</subject><subject>DNA</subject><subject>DNA repair</subject><subject>Environmental aspects</subject><subject>Enzymes</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic polymorphism</subject><subject>Genetic polymorphisms</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Glutathione</subject><subject>Glutathione transferase</subject><subject>Glutathione Transferase - genetics</subject><subject>Health</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Intervals</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Maria</subject><subject>Mathematical models</subject><subject>Middle Aged</subject><subject>Neoplasms - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Risk</subject><subject>Risk factors</subject><subject>Tobacco smoking</subject><issn>0091-6765</issn><issn>1552-9924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN091u0zAUB_AIgdgYXPAAIIuLIS5aYsex4xukqmKl0mBoK9xajnPSuCR2sVOgL8Bz435orKgClItE8c9_5fjkJMlTnA4xKcRraJZDjDkT95JTnOdkIASh95PTNBV4wDjLT5JHISzSNMUFYw-TEywIT3khTpOfoxCcNqo3zqIS-u8AFl14-LoCq9fI1WjceNe54DrVolEJ3m9tQMpWaKysBo-uTfiCpgF9cD2a2rrd7IUKlWs0AQu90eija9ed88vGhC4gY9HkZvYebzPi0ww_Th7Uqg3wZH8_Sz5dvJ2N3w0urybT8ehyoJkg_SCHvKKsrlQRKwNWVilwXKhK06JIeZ6ByFnONBdVUVcFBs7qXOCqJhWjHOsyO0ve7HKXq7KDSoPtvWrl0ptO-bV0ysjDFWsaOXffJGFUEIJjwMt9gHfxjEIvOxM0tK2y4FZBcppRnhWURHn-VxnDuKBC_BumGcsyQSN88QdcuJW38bwkIfEDOaEbNNihuWpBGlu7WIeexz7EcpyF2sTXIyxoTgTFGz884uNVQWf00Q2vDjZE08OPfq5WIcjpzfX_26vPh_b8jm1AtX0TXLva_m1HQ7V3IXiob9uHU7mZBxnnQW7nIdrnd_v9W-4HIIJnO7AIvfO36ySPfRSEZb8ACygMug</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Rossi, Anna Maria</creator><creator>Hansteen, Inger-Lise</creator><creator>Skjelbred, Camilla Furu</creator><creator>Ballardin, Michela</creator><creator>Maggini, Valentina</creator><creator>Murgia, Elena</creator><creator>Tomei, Antonio</creator><creator>Viarengo, Paolo</creator><creator>Knudsen, Lisbeth E.</creator><creator>Barale, Roberto</creator><creator>Norppa, Hannu</creator><creator>Bonassi, Stefano</creator><general>National Institute of Environmental Health Sciences. 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between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1</title><author>Rossi, Anna Maria ; Hansteen, Inger-Lise ; Skjelbred, Camilla Furu ; Ballardin, Michela ; Maggini, Valentina ; Murgia, Elena ; Tomei, Antonio ; Viarengo, Paolo ; Knudsen, Lisbeth E. ; Barale, Roberto ; Norppa, Hannu ; Bonassi, Stefano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5e5d46fda8091e6bd0e718adc4880753e95656c79d8fd81e76f591df2d6471cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aberration</topic><topic>Adult</topic><topic>Bayesian analysis</topic><topic>Biological markers</topic><topic>Blood</topic><topic>Cancer</topic><topic>Case control studies</topic><topic>Chromosome Aberrations</topic><topic>Chromosome abnormalities</topic><topic>Control</topic><topic>Control 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Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1</atitle><jtitle>Environmental health perspectives</jtitle><addtitle>Environ Health Perspect</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>117</volume><issue>2</issue><spage>203</spage><epage>208</epage><pages>203-208</pages><issn>0091-6765</issn><eissn>1552-9924</eissn><abstract>Background: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. Objectives: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. Methods: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. Results: The association between CA frequency and cancer risk was confirmed [${\rm OR}_{\text{medium}}$
$(\text{odds ratio})_{\text{medium}}=1.5$, 95% credibility interval (CrI), 0.9-2.5;${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (${\rm OR}_{\text{high}}=9.4$, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (${\rm OR}_{\text{high}}=6.2$, 95% CrI, 1.5-20.0), the genitourinary tract (${\rm OR}_{\text{high}}=4.0$, 95% CrI, 1.4-10.0), and the digestive tract (${\rm OR}_{\text{high}}=2.8$, 95% CrI, 1.2-5.8). Conclusions: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</pub><pmid>19270789</pmid><doi>10.1289/ehp.11769</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Environmental health perspectives, 2009-02, Vol.117 (2), p.203-208 |
| issn | 0091-6765 1552-9924 |
| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Aberration Adult Bayesian analysis Biological markers Blood Cancer Case control studies Chromosome Aberrations Chromosome abnormalities Control Control equipment Copyrights Cytogenetics DNA DNA repair Environmental aspects Enzymes Female Genetic aspects Genetic polymorphism Genetic polymorphisms Genetic Predisposition to Disease - genetics Genetics Genotype Genotypes Glutathione Glutathione transferase Glutathione Transferase - genetics Health Health aspects Humans Intervals Lymphocytes Male Maria Mathematical models Middle Aged Neoplasms - genetics Polymorphism Polymorphism, Genetic - genetics Risk Risk factors Tobacco smoking |
| title | Association between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T23%3A58%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20between%20Frequency%20of%20Chromosomal%20Aberrations%20and%20Cancer%20Risk%20Is%20Not%20Influenced%20by%20Genetic%20Polymorphisms%20in%20GSTM1%20and%20GSTT1&rft.jtitle=Environmental%20health%20perspectives&rft.au=Rossi,%20Anna%20Maria&rft.date=2009-02-01&rft.volume=117&rft.issue=2&rft.spage=203&rft.epage=208&rft.pages=203-208&rft.issn=0091-6765&rft.eissn=1552-9924&rft_id=info:doi/10.1289/ehp.11769&rft_dat=%3Cgale_pubme%3EA194529414%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222647244&rft_id=info:pmid/19270789&rft_galeid=A194529414&rft_jstor_id=25434926&rfr_iscdi=true |