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dc.contributor.authorCanova, Cristina
dc.contributor.authorHashibe, Mia
dc.contributor.authorSimonato, Lorenzo
dc.contributor.authorNelis, Mari
dc.contributor.authorMetspalu, Andres
dc.contributor.authorLagiou, Pagona
dc.contributor.authorTrichopoulos, Dimitrios
dc.contributor.authorAhrens, Wolfgang
dc.contributor.authorPigeot, Iris
dc.contributor.authorMerletti, Franco
dc.contributor.authorRichiardi, Lorenzo
dc.contributor.authorTalamini, Renato
dc.contributor.authorBarzan, Luigi
dc.contributor.authorMacfarlane, Gary J
dc.contributor.authorMacfarlane, Tatiana V
dc.contributor.authorHolcátová, Ivana
dc.contributor.authorBencko, Vladimir
dc.contributor.authorBenhamou, Simone
dc.contributor.authorBouchardy, Christine
dc.contributor.authorKjaerheim, Kristina
dc.contributor.authorLowry, Ray
dc.contributor.authorAgudo, Antonio
dc.contributor.authorCastellsagué, Xavier
dc.contributor.authorConway, David I
dc.contributor.authorMcKinney, Patricia A
dc.contributor.authorZnaor, Ariana
dc.contributor.authorMcCartan, Bernard E
dc.contributor.authorHealy, Claire M
dc.contributor.authorMarron, Manuela
dc.contributor.authorBrennan, Paul
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
html.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.


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