Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.

Hdl Handle:
http://hdl.handle.net/10147/124012
Title:
Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.
Authors:
Canova, Cristina; Hashibe, Mia; Simonato, Lorenzo; Nelis, Mari; Metspalu, Andres; Lagiou, Pagona; Trichopoulos, Dimitrios; Ahrens, Wolfgang; Pigeot, Iris; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Macfarlane, Gary J; Macfarlane, Tatiana V; Holcátová, Ivana; Bencko, Vladimir; Benhamou, Simone; Bouchardy, Christine; Kjaerheim, Kristina; Lowry, Ray; Agudo, Antonio; Castellsagué, Xavier; Conway, David I; McKinney, Patricia A; Znaor, Ariana; McCartan, Bernard E; Healy, Claire M; Marron, Manuela; Brennan, Paul
Affiliation:
Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy.
Citation:
Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project. 2009, 69 (7):2956-65 Cancer Res.
Journal:
Cancer research
Issue Date:
1-Apr-2009
URI:
http://hdl.handle.net/10147/124012
DOI:
10.1158/0008-5472.CAN-08-2604
PubMed ID:
19339270
Abstract:
Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Alcohol Drinking; Case-Control Studies; DNA Repair; Esophageal Neoplasms; Europe; Female; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms; Polymorphism, Single Nucleotide; Smoking
ISSN:
1538-7445

Full metadata record

DC FieldValue Language
dc.contributor.authorCanova, Cristinaen
dc.contributor.authorHashibe, Miaen
dc.contributor.authorSimonato, Lorenzoen
dc.contributor.authorNelis, Marien
dc.contributor.authorMetspalu, Andresen
dc.contributor.authorLagiou, Pagonaen
dc.contributor.authorTrichopoulos, Dimitriosen
dc.contributor.authorAhrens, Wolfgangen
dc.contributor.authorPigeot, Irisen
dc.contributor.authorMerletti, Francoen
dc.contributor.authorRichiardi, Lorenzoen
dc.contributor.authorTalamini, Renatoen
dc.contributor.authorBarzan, Luigien
dc.contributor.authorMacfarlane, Gary Jen
dc.contributor.authorMacfarlane, Tatiana Ven
dc.contributor.authorHolcátová, Ivanaen
dc.contributor.authorBencko, Vladimiren
dc.contributor.authorBenhamou, Simoneen
dc.contributor.authorBouchardy, Christineen
dc.contributor.authorKjaerheim, Kristinaen
dc.contributor.authorLowry, Rayen
dc.contributor.authorAgudo, Antonioen
dc.contributor.authorCastellsagué, Xavieren
dc.contributor.authorConway, David Ien
dc.contributor.authorMcKinney, Patricia Aen
dc.contributor.authorZnaor, Arianaen
dc.contributor.authorMcCartan, Bernard Een
dc.contributor.authorHealy, Claire Men
dc.contributor.authorMarron, Manuelaen
dc.contributor.authorBrennan, Paulen
dc.date.accessioned2011-03-09T11:51:17Z-
dc.date.available2011-03-09T11:51:17Z-
dc.date.issued2009-04-01-
dc.identifier.citationGenetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project. 2009, 69 (7):2956-65 Cancer Res.en
dc.identifier.issn1538-7445-
dc.identifier.pmid19339270-
dc.identifier.doi10.1158/0008-5472.CAN-08-2604-
dc.identifier.urihttp://hdl.handle.net/10147/124012-
dc.description.abstractCancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.-
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAlcohol Drinking-
dc.subject.meshCase-Control Studies-
dc.subject.meshDNA Repair-
dc.subject.meshEsophageal Neoplasms-
dc.subject.meshEurope-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHead and Neck Neoplasms-
dc.subject.meshHumans-
dc.subject.meshLaryngeal Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMouth Neoplasms-
dc.subject.meshPharyngeal Neoplasms-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshSmoking-
dc.titleGenetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.en
dc.typeArticleen
dc.contributor.departmentDepartment of Environmental Medicine and Public Health, University of Padova, Padova, Italy.en
dc.identifier.journalCancer researchen
dc.description.provinceLeinster-

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