TY - JOUR
T1 - Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 european countries
T2 - The ARCAGE project
AU - Canova, Cristina
AU - Hashibe, Mia
AU - Simonato, Lorenzo
AU - Nelis, Mari
AU - Metspalu, Andres
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Ahrens, Wolfgang
AU - Pigeot, Iris
AU - Merletti, Franco
AU - Richiardi, Lorenzo
AU - Talamini, Renato
AU - Barzan, Luigi
AU - Macfarlane, Gary J.
AU - Macfarlane, Tatiana V.
AU - Holcátová, Ivana
AU - Bencko, Vladimir
AU - Benhamou, Simone
AU - Bouchardy, Christine
AU - Kjaerheim, Kristina
AU - Lowry, Ray
AU - Agudo, Antonio
AU - Castellsagué, Xavier
AU - Conway, David I.
AU - McKinney, Patricia A.
AU - Znaor, Ariana
AU - McCartan, Bernard E.
AU - Healy, Claire M.
AU - Marron, Manuela
AU - Brennan, Paul
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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 (SNF) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNFs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false- positive results, we focused on SNPs in CÏP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASCl), 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 (rsl800610), the P trend was 0.007. Variants in two SNPs of GASCl 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.
AB - 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 (SNF) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNFs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false- positive results, we focused on SNPs in CÏP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASCl), 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 (rsl800610), the P trend was 0.007. Variants in two SNPs of GASCl 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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U2 - 10.1158/0008-5472.CAN-08-2604
DO - 10.1158/0008-5472.CAN-08-2604
M3 - Article
C2 - 19339270
AN - SCOPUS:66149155873
VL - 69
SP - 2956
EP - 2965
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 7
ER -