학술논문
The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract.
Document Type
Article
Author
Delahaye-Sourdeix, Manon; Oliver, Javier; 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.
Source
Subject
*LOCUS (Genetics)
*DISEASE susceptibility
*SQUAMOUS cell carcinoma
*LUNG cancer
*GENE expression
ALIMENTARY canal cancer
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]