Evidence of gene gene interactions in lung carcinogenesis in a large pooled analysis.

2.50
Hdl Handle:
http://hdl.handle.net/10146/38096
Title:
Evidence of gene gene interactions in lung carcinogenesis in a large pooled analysis.
Authors:
Vineis, Paolo; Anttila, Sisko; Benhamou, Simone; Spinola, Monica; Hirvonen, Ari; Kiyohara, Chikako; Garte, Seymour J.; Puntoni, Riccardo; Rannug, Agneta; Strange, Richard C.; Taioli, Emanuela
Abstract:
To test the hypothesis of interaction among genetic variants in increasing the individual risk of cancer, we have studied the cumulative effect on lung cancer risk of variants in three metabolic genes, CYP1A1, GSTM1 and GSTT1, which are involved in the metabolism of the tobacco smoke constituents and environmental contaminants, polycyclic aromatic hydrocarbons and of other lung carcinogens. We have selected from the Genetic Susceptibility to Environmental Carcinogens pooled analysis all the studies on lung cancer conducted after 1991 in which all variants were available. The data set includes 611 cases and 870 controls. We found a cumulative effect of the combination of the a priori 'at-risk' alleles for these genes (P for trend 0.004). The risk of lung cancer was increased with the combination of CYP1A1*2B or CYP1A1*4 alleles and the double deletion of both GSTM1 and GSTT1 up to an odds ratio (OR) of 8.25 (95% confidence interval 2.29-29.77) for the combination including CYP1A1*4; among never smokers, the latter combination was associated with an OR of 16.19 (1.90-137). Estimates did not change after adjustment by the number of cigarettes smoked and duration of smoking were consistent across ethnicities and were approximately the same for adenocarcinomas and squamous cell carcinomas. These observations from a large pooled analysis strongly suggest the existence of gene-gene interactions in lung carcinogenesis. People with rare combinations of common gene variants have a high risk of cancer and can be assimilated to subjects with highly penetrant mutations.
Citation:
Carcinogenesis 2007, 28 (9):1902-1905
Journal:
Carcinogenesis
Issue Date:
Sep-2007
URI:
http://hdl.handle.net/10146/38096
DOI:
10.1093/carcin/bgm039
PubMed ID:
17307802
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/28/9/1902
Type:
Article
Language:
en
ISSN:
0143-3334
Sponsors:
This study has been made possible by a grant of the Compagnia di San Paolo to the ISI Foundation, Torino, by a grant from the European Commission to E.T. (CAN/96/33919), by a grant from the Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC), and to the Environmental Cancer Risk, Nutrition, Individual Suscriptibility (ECNIS) Network of Excellence (grant FOOD-CT-2005-513943) (WP8) and NIH P50CA090440-07.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorVineis, Paolo-
dc.contributor.authorAnttila, Sisko-
dc.contributor.authorBenhamou, Simone-
dc.contributor.authorSpinola, Monica-
dc.contributor.authorHirvonen, Ari-
dc.contributor.authorKiyohara, Chikako-
dc.contributor.authorGarte, Seymour J.-
dc.contributor.authorPuntoni, Riccardo-
dc.contributor.authorRannug, Agneta-
dc.contributor.authorStrange, Richard C.-
dc.contributor.authorTaioli, Emanuela-
dc.date.accessioned2008-09-24T08:14:57Z-
dc.date.available2008-09-24T08:14:57Z-
dc.date.issued2007-09-
dc.identifier.citationCarcinogenesis 2007, 28 (9):1902-1905en
dc.identifier.issn0143-3334-
dc.identifier.pmid17307802-
dc.identifier.doi10.1093/carcin/bgm039-
dc.identifier.urihttp://hdl.handle.net/10146/38096-
dc.description.abstractTo test the hypothesis of interaction among genetic variants in increasing the individual risk of cancer, we have studied the cumulative effect on lung cancer risk of variants in three metabolic genes, CYP1A1, GSTM1 and GSTT1, which are involved in the metabolism of the tobacco smoke constituents and environmental contaminants, polycyclic aromatic hydrocarbons and of other lung carcinogens. We have selected from the Genetic Susceptibility to Environmental Carcinogens pooled analysis all the studies on lung cancer conducted after 1991 in which all variants were available. The data set includes 611 cases and 870 controls. We found a cumulative effect of the combination of the a priori 'at-risk' alleles for these genes (P for trend 0.004). The risk of lung cancer was increased with the combination of CYP1A1*2B or CYP1A1*4 alleles and the double deletion of both GSTM1 and GSTT1 up to an odds ratio (OR) of 8.25 (95% confidence interval 2.29-29.77) for the combination including CYP1A1*4; among never smokers, the latter combination was associated with an OR of 16.19 (1.90-137). Estimates did not change after adjustment by the number of cigarettes smoked and duration of smoking were consistent across ethnicities and were approximately the same for adenocarcinomas and squamous cell carcinomas. These observations from a large pooled analysis strongly suggest the existence of gene-gene interactions in lung carcinogenesis. People with rare combinations of common gene variants have a high risk of cancer and can be assimilated to subjects with highly penetrant mutations.en
dc.description.sponsorshipThis study has been made possible by a grant of the Compagnia di San Paolo to the ISI Foundation, Torino, by a grant from the European Commission to E.T. (CAN/96/33919), by a grant from the Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC), and to the Environmental Cancer Risk, Nutrition, Individual Suscriptibility (ECNIS) Network of Excellence (grant FOOD-CT-2005-513943) (WP8) and NIH P50CA090440-07.en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/28/9/1902en
dc.subject.meshConfidence Intervals-
dc.subject.meshCytochrome P-450 CYP1A1-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGlutathione Transferase-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshOdds Ratio-
dc.subject.meshReference Values-
dc.subject.meshRisk Factors-
dc.subject.meshSmoking-
dc.subject.meshVariation (Genetics)-
dc.titleEvidence of gene gene interactions in lung carcinogenesis in a large pooled analysis.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen

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