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

Canova, C. et al. (2009) Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project. Cancer Research, 69(7), pp. 2956-2965. (doi:10.1158/0008-5472.CAN-08-2604)

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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. [Cancer Res 2009;69(7):2956–65]

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Conway, Professor David
Authors: Canova, C., Hashibe, M., Simonato, L., Nelis, M., Metspalu, A., Lagiou, P., Trichopoulos, D., Ahrens, W., Pigeot, I., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Macfarlane, G. J., Macfarlane, T. V., Holcatova, I., Bencko, V., Benhamou, S., Bouchardy, C., Kjaerheim, K., Lowry, R., Agudo, A., Castellsague, X., Conway, D. I., McKinney, P. A., Znaor, A., McCartan, B. E., Healy, C. M., Marron, M., and Brennan, P.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Cancer Research
ISSN:0008-5472
ISSN (Online):1538-7445
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