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

by Lener, Marcin , Curado, Maria Paula , Agudo, Antonio , Menezes, Ana , Lagiou, Pagona , Richiardi, Lorenzo , Macfarlane, Tatiana V. , Mates, Ioan Nicolae , Janout, Vladimir , Healy, Claire M. , Brenner, Darren R. , Eluf-Neto, José , Timofeeva, Maria N. , Conway, David I. , Fabianova, Eleonora , Canova, Cristina , Wünsch-Filho, Victor , McKay, James D. , Samant, Tanuja A. , Byrnes, Graham , Jaworowska, Ewa , Oliver, Javier , Kjaerheim, Kristina , Rajkumar, Thangarajan , Barzan, Luigi , Szeszenia-Dabrowska, Neonilia , Bencko, Vladimir , Lubiński, Jan , Franceschi, Silvia , Anantharaman, Devasena , Lissowska, Jolanta , Gaborieau, Valérie , Thakker, Nalin S. , Boccia, Stefania , Vallée, Maxime P. , Delahaye-Sourdeix, Manon , Wozniak, Magdalena B. , Serraino, Diego , Garrote, Leticia Fernández , Chabrier, Amélie , Johansson, Mattias , Ahrens, Wolfgang , Zaridze, David , Foretova, Lenka , Koifman, Sergio , Brennan, Paul , Mahimkar, Manoj B. , Castellsagué, Xavier , Holcátová, Ivana , Boffetta, Paolo , Znaor, Ariana , Matsuo, Keitaro

in Alcohol / Bioinformatics / Cancer / Carcinoma, Squamous Cell - genetics / Case-Control Studies / Cell cycle / Chromosome 12 / Chromosomes, Human, Pair 12 - genetics / Computer Simulation / Copy number / Demography / Dentistry / Deoxyribonucleic acid / Disease susceptibility / DNA / Epidemiology / Female / Gene expression / Genetic aspects / Genetic diversity / Genetic Loci / Genetic Predisposition to Disease / Genetic variance / Genetics / Genomes / Germ Cells / Head and Neck Neoplasms - genetics / Health risk assessment / Humans / Hygiene / Life Sciences / Loci / Lung cancer / Lung carcinoma / Lung Neoplasms - genetics / Male / Medical research / Medicine / Middle Aged / Oncology / Pathology / Physical Chromosome Mapping / Polymorphism, Single Nucleotide - genetics / Public health / Quantitative Trait Loci - genetics / Rad52 DNA Repair and Recombination Protein - genetics / Rad52 protein / Risk Factors / Santé publique et épidémiologie / Squamous cell carcinoma / Tumorigenesis / Tumors

2015

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

2015

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

2015

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Journal Article

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

Lener, Marcin,

Curado, Maria Paula,

Agudo, Antonio,

Menezes, Ana,

Lagiou, Pagona,

Richiardi, Lorenzo,

Macfarlane, Tatiana V.,

Mates, Ioan Nicolae,

Janout, Vladimir,

Healy, Claire M.,

Brenner, Darren R.,

Eluf-Neto, José,

Timofeeva, Maria N.,

Conway, David I.,

Fabianova, Eleonora,

Canova, Cristina,

Wünsch-Filho, Victor,

McKay, James D.,

Samant, Tanuja A.,

Byrnes, Graham,

Jaworowska, Ewa,

Oliver, Javier,

Kjaerheim, Kristina,

Rajkumar, Thangarajan,

Barzan, Luigi,

Szeszenia-Dabrowska, Neonilia,

Bencko, Vladimir,

Lubiński, Jan,

Franceschi, Silvia,

Anantharaman, Devasena,

Lissowska, Jolanta,

Gaborieau, Valérie,

Thakker, Nalin S.,

Boccia, Stefania,

Vallée, Maxime P.,

Delahaye-Sourdeix, Manon,

Wozniak, Magdalena B.,

Serraino, Diego,

Garrote, Leticia Fernández,

Chabrier, Amélie,

Johansson, Mattias,

Ahrens, Wolfgang,

Zaridze, David,

Foretova, Lenka,

Koifman, Sergio,

Brennan, Paul,

Mahimkar, Manoj B.,

Castellsagué, Xavier,

Holcátová, Ivana,

Boffetta, Paolo,

Znaor, Ariana,

Matsuo, Keitaro

2015

Overview

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.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Alcohol

/ Bioinformatics

/ Cancer

/ Carcinoma, Squamous Cell - genetics

/ Case-Control Studies

/ Cell cycle

/ Chromosome 12