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