The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Delahaye-Sourdeix, M. et al. (2015) The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract. PLoS ONE, 10(3), e0117639. (doi: 10.1371/journal.pone.0117639) (PMID:25793373) (PMCID:PMC4368781)

Abstract

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04–1.15, p = 6x10−4). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10−3) and LUSC (p = 9x10−4) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10−48 and p = 3x10−29 in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Conway, Professor David
• Authors: Delahaye-Sourdeix, M., Oliver, J., Timofeeva, M. N., Gaborieau, V., Johansson, M., Chabrier, A., Wozniak, M. B., Brenner, D. R., Vallée, M. P., Anantharaman, D., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T. V., Barzan, L., Canova, C., Thakker, N. S., Conway, D. I., Znaor, A., Healy, C. M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Mates, I. N., Bencko, V., Foretova, L., Janout, V., Curado, M. P., Koifman, S., Menezes, A., Wünsch-Filho, V., Eluf-Neto, J., Boffetta, P., Garrote, L. F., Serraino, D., Lener, M., Jaworowska, E., Lubiński, J., Boccia, S., Rajkumar, T., Samant, T. A., Mahimkar, M. B., Matsuo, K., Franceschi, S., Byrnes, G., Brennan, P., and McKay, J. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2015 Delahaye-Sourdeix et al.
• First Published: First published in PLoS ONE 10(3):e0117639
• Publisher Policy: Reproduced under a Creative Commons License