Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPDELAHAYE-SOURDEIX, ManonOLIVER, JavierTIMOFEEVA, Maria N.GABORIEAU, ValerieJOHANSSON, MattiasCHABRIER, AmelieWOZNIAK, Magdalena B.BRENNER, Darren R.VALLEE, Maxime P.ANANTHARAMAN, DevasenaLAGIOU, PagonaHOLCATOVA, IvanaRICHIARDI, LorenzoKJAERHEIM, KristinaAGUDO, AntonioCASTELLSAGUE, XavierMACFARLANE, Tatiana V.BARZAN, LuigiCANOVA, CristinaTHAKKER, Nalin S.CONWAY, David I.ZNAOR, ArianaHEALY, Claire M.AHRENS, WolfgangZARIDZE, DavidSZESZENIA-DABROWSKA, NeoniliaLISSOWSKA, JolantaFABIANOVA, EleonoraMATES, Ioan NicolaeBENCKO, VladimirFORETOVA, LenkaJANOUT, VladimirCURADO, Maria PaulaKOIFMAN, SergioMENEZES, AnaWUENSCH-FILHO, VictorELUF-NETO, JoseBOFFETTA, PaoloGARROTE, Leticia FernandezSERRAINO, DiegoLENER, MarcinJAWOROWSKA, EwaLUBINSKI, JanBOCCIA, StefaniaRAJKUMAR, ThangarajanSAMANT, Tanuja A.MAHIMKAR, Manoj B.MATSUO, KeitaroFRANCESCHI, SilviaBYRNES, GrahamBRENNAN, PaulMCKAY, James D.2015-10-262015-10-262015PLOS ONE, v.10, n.3, article ID e0117639, 12p, 20151932-6203https://observatorio.fm.usp.br/handle/OPI/11770Genetic 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.engopenAccessdifferential expression analysisgenome-wide associationhomologous recombinationsynthetically lethalrad52 inactivationbreak repairlung-cancerrna-seqriskbrca2articleCopyright PUBLIC LIBRARY SCIENCE10.1371/journal.pone.0117639Multidisciplinary Sciences