The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

• Authors: DELAHAYE-SOURDEIX Manon; OLIVER Chavier; TIMOFEEVA Maria N.; GABORIEAU Valérie; JOHANSSON Mattias; CHABRIER Amélie; WOZNIAK Magdalena B.; BRENNER Darren R.; VALLÉE 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 Neonilia; LISSOWSKA Jolanta; FABIANOVA Eleonora; MATES Ioan Nicolae; BENCKO Vladimir; FORETOVÁ Lenka; JANOUT Vladimir; CURADO Maria Paula; KOIFMAN Sergio; MENEZES Ana; WÜNSCH-FILHO Victor; ELUF-NETO José; BOFFETTA Paolo; GARROTE Leticia Fernández; SERRAINO Diego; LENER Marcin; JAWOROWSKA Ewa; LUBINSKI Jan; BOCCIA Stefania; RAJKUMAR Thangarajan; SAMANT Tanuja Graham; MAHIMKAR Manoj B.; MATSUO Keitaro; FRANCESCHI Silvia; BYRNES Graham; BRENNAN Paul; MCKAY James D.
• Year of publication: 2015
• Type: Article in Periodical
• Magazine / Source: Plos one
• MU Faculty or unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1371/journal.pone.0117639
• Field: Oncology and hematology
• Keywords: DIFFERENTIAL EXPRESSION ANALYSIS; GENOME-WIDE ASSOCIATION; HOMOLOGOUS RECOMBINATION; SYNTHETICALLY LETHAL; RAD52 INACTIVATION; BREAK REPAIR; LUNG-CANCER; RNA-SEQ; RISK; BRCA2
• Description: 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.