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.

Item Type: Article
Additional Information: Copyright: © 2015 Delahaye-Sourdeix et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
MeSH: Carcinoma, Squamous Cell/genetics ; Case-Control Studies ; Chromosomes, Human, Pair 12/genetics ; Computer Simulation ; Demography ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Germ Cells ; Head and Neck Neoplasms/genetics ; Humans ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Physical Chromosome Mapping ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Rad52 DNA Repair and Recombination Protein/genetics ; Risk Factors
Departments: Katedra za medicinsku statistiku, epidemiologiju i medicinsku informatiku
Depositing User: Marijan Šember
Status: Published
Creators:
CreatorsEmail
Delahaye-Sourdeix, ManonUNSPECIFIED
Oliver, JavierUNSPECIFIED
Timofeeva, Maria N.UNSPECIFIED
Gaborieau, ValérieUNSPECIFIED
Johansson, MattiasUNSPECIFIED
Chabrier, AmélieUNSPECIFIED
Wozniak, Magdalena B.UNSPECIFIED
Brenner, Darren R.UNSPECIFIED
Vallée, Maxime P.UNSPECIFIED
Anantharaman, DevasenaUNSPECIFIED
Lagiou, PagonaUNSPECIFIED
Holcátová, IvanaUNSPECIFIED
Richiardi, LorenzoUNSPECIFIED
Kjaerheim, KristinaUNSPECIFIED
Agudo, AntonioUNSPECIFIED
Castellsagué, XavierUNSPECIFIED
Macfarlane, Tatiana V.UNSPECIFIED
Barzan, LuigiUNSPECIFIED
Canova, CristinaUNSPECIFIED
Thakker, Nalin S.UNSPECIFIED
Conway, David I.UNSPECIFIED
Znaor, ArianaUNSPECIFIED
Healy, Claire M.UNSPECIFIED
Ahrens, WolfgangUNSPECIFIED
Zaridze, DavidUNSPECIFIED
Szeszenia-Dabrowska, NeoniliaUNSPECIFIED
Lissowska, JolantaUNSPECIFIED
Fabianova, EleonoraUNSPECIFIED
Mates, Ioan NicolaeUNSPECIFIED
Bencko, VladimirUNSPECIFIED
Foretova, LenkaUNSPECIFIED
Janout, VladimirUNSPECIFIED
Curado, Maria PaulaUNSPECIFIED
Koifman, SergioUNSPECIFIED
Menezes, AnaUNSPECIFIED
Wünsch-Filho, VictorUNSPECIFIED
Eluf-Neto, JoséUNSPECIFIED
Boffetta, PaoloUNSPECIFIED
Garrote, Leticia FernándezUNSPECIFIED
Serraino, DiegoUNSPECIFIED
Lener, MarcinUNSPECIFIED
Jaworowska, EwaUNSPECIFIED
Lubiński, JanUNSPECIFIED
Boccia, StefaniaUNSPECIFIED
Rajkumar, ThangarajanUNSPECIFIED
Samant, Tanuja A.UNSPECIFIED
Mahimkar, Manoj B.UNSPECIFIED
Matsuo, KeitaroUNSPECIFIED
Franceschi, SilviaUNSPECIFIED
Byrnes, GrahamUNSPECIFIED
Brennan, PaulUNSPECIFIED
McKay, James D.UNSPECIFIED
Date: 20 March 2015
Date Deposited: 27 Jan 2016 09:05
Last Modified: 27 Jan 2016 09:05
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2382

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