TY - JOUR
T1 - The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract
AU - Delahaye-Sourdeix, Manon
AU - Oliver, Javier
AU - Timofeeva, Maria N.
AU - Gaborieau, Valérie
AU - Johansson, Mattias
AU - Chabrier, Amélie
AU - Wozniak, Magdalena B.
AU - Brenner, Darren R.
AU - Vallée, Maxime P.
AU - Anantharaman, Devasena
AU - Lagiou, Pagona
AU - Holcátová, Ivana
AU - Richiardi, Lorenzo
AU - Kjaerheim, Kristina
AU - Agudo, Antonio
AU - Castellsagué, Xavier
AU - Macfarlane, Tatiana V.
AU - Barzan, Luigi
AU - Canova, Cristina
AU - Thakker, Nalin S.
AU - Conway, David I.
AU - Znaor, Ariana
AU - Healy, Claire M.
AU - Ahrens, Wolfgang
AU - Zaridze, David
AU - Szeszenia-Dabrowska, Neonilia
AU - Lissowska, Jolanta
AU - Fabianova, Eleonora
AU - Mates, Ioan Nicolae
AU - Bencko, Vladimir
AU - Foretova, Lenka
AU - Janout, Vladimir
AU - Curado, Maria Paula
AU - Koifman, Sergio
AU - Menezes, Ana
AU - Wünsch-Filho, Victor
AU - Eluf-Neto, José
AU - Boffetta, Paolo
AU - Garrote, Leticia Fernández
AU - Serraino, Diego
AU - Lener, Marcin
AU - Jaworowska, Ewa
AU - Lubiński, Jan
AU - Boccia, Stefania
AU - Rajkumar, Thangarajan
AU - Samant, Tanuja A.
AU - Mahimkar, Manoj B.
AU - Matsuo, Keitaro
AU - Franceschi, Silvia
AU - Byrnes, Graham
AU - Brennan, Paul
AU - Mckay, James D.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - BRCA2
KW - BREAK REPAIR
KW - DIFFERENTIAL EXPRESSION ANALYSIS
KW - GENOME-WIDE ASSOCIATION
KW - HOMOLOGOUS RECOMBINATION
KW - LUNG-Cancer
KW - RAD52 INACTIVATION
KW - RNA-SEQ
KW - BRCA2
KW - BREAK REPAIR
KW - DIFFERENTIAL EXPRESSION ANALYSIS
KW - GENOME-WIDE ASSOCIATION
KW - HOMOLOGOUS RECOMBINATION
KW - LUNG-Cancer
KW - RAD52 INACTIVATION
KW - RNA-SEQ
UR - http://hdl.handle.net/10807/70404
U2 - 10.1371/journal.pone.0117639
DO - 10.1371/journal.pone.0117639
M3 - Article
SN - 1932-6203
VL - 10
SP - e0117639-e0117639
JO - PLoS One
JF - PLoS One
ER -
