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

Delahaye-Sourdeix, Manon and Oliver, Javier and Timofeeva, Maria N. and Gaborieau, Valérie and Johansson, Mattias and Chabrier, Amélie and Wozniak, Magdalena B. and Brenner, Darren R. and Vallée, Maxime P. and Anantharaman, Devasena and Lagiou, Pagona and Holcátová, Ivana and Richiardi, Lorenzo and Kjaerheim, Kristina and Agudo, Antonio and Castellsagué, Xavier and Macfarlane, Tatiana V. and Barzan, Luigi and Canova, Cristina and Thakker, Nalin S. and Conway, David I. and Znaor, Ariana and Healy, Claire M. and Ahrens, Wolfgang and Zaridze, David and Szeszenia-Dabrowska, Neonilia and Lissowska, Jolanta and Fabianova, Eleonora and Mates, Ioan Nicolae and Bencko, Vladimir and Foretova, Lenka and Janout, Vladimir and Curado, Maria Paula and Koifman, Sergio and Menezes, Ana and Wünsch-Filho, Victor and Eluf-Neto, José and Boffetta, Paolo and Garrote, Leticia Fernández and Serraino, Diego and Lener, Marcin and Jaworowska, Ewa and Lubiński, Jan and Boccia, Stefania and Rajkumar, Thangarajan and Samant, Tanuja A. and Mahimkar, Manoj B. and Matsuo, Keitaro and Franceschi, Silvia and Byrnes, Graham and Brennan, Paul and McKay, James D. (2015) The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract. PLoS One, 10 (3). e0117639. ISSN 1932-6203

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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.

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