The 12p13.33/rad52 Locus And Genetic Susceptibility To Squamous Cell Cancers Of Upper Aerodigestive Tract

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...

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Authors: Delahaye-Sourdeix, Manon; Oliver, Javier; Timofeeva, Maria N.; Gaborieau, Valérie; Johansson, Mattias; Chabrier, Amélie; Wozniak, Magdalena B.; Brenner, Darren R.; Vallee, Maxime P.; Anantharaman, Devasena; Lagiou, Pagona; Holcátová, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsagué, Xavier; MacFarlane, Tatiana V.; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S.; Conway, David I.; Znaor, Ariana; Healy, Claire M.; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Fabianova, Eleonora; Mates, Ioan Nicolae; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana A.; Wünsch-Filho, Victor; Eluf Neto, José; Boffetta, Paolo; Fernández Garrote, Leticia; Serraino, Diego; Lener, Marcin; Jaworowska, Ewa; Lubinski, Jan; Boccia, Stefania; Rajkumar, Thangarajan; Samant, Tanuja A.; Mahimkar, Manoj B.; Matsuo, Keitaro; Franceschi, Silvia; Byrnes, Graham; Brennan, Paul; McKay, James D.
Format: Article
Status:Published version
Publication date:2015
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/124339
Online Access:https://hdl.handle.net/2445/124339
Access Level:Open access
Keyword:Càncer de pulmó
Expressió gènica
Lung cancer
Gene expression
Summary: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.

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