The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

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

doi:10.1371/journal.pone.0117639

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

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 ThakkerDavid 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

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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.

Original language	English
Pages (from-to)	e0117639
Journal	PLoS ONE
Volume	10
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0117639
Publication status	Published - 20 Mar 2015

Keywords

Carcinoma, Squamous Cell
Case-Control Studies
Chromosomes, Human, Pair 12
Computer Simulation
Demography
Female
Genetic Loci
Genetic Predisposition to Disease
Germ Cells
Head and Neck Neoplasms
Humans
Lung Neoplasms
Male
Middle Aged
Physical Chromosome Mapping
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Rad52 DNA Repair and Recombination Protein
Risk Factors
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Final Published VersionFinal published version, 1.11 MBLicence: CC BY

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Delahaye-Sourdeix, M., Oliver, J., Timofeeva, M. N., Gaborieau, V., Johansson, M., Chabrier, A., Wozniak, M. B., Brenner, D. R., Vallée, M. P., Anantharaman, D., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T. V., Barzan, L., Canova, C., ... McKay, J. D. (2015). The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract. PLoS ONE, 10(3), e0117639. https://doi.org/10.1371/journal.pone.0117639

@article{b9f9eebe26d34e7786621fdf9781fd1b,

title = "The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract",

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.",

keywords = "Carcinoma, Squamous Cell, Case-Control Studies, Chromosomes, Human, Pair 12, Computer Simulation, Demography, Female, Genetic Loci, Genetic Predisposition to Disease, Germ Cells, Head and Neck Neoplasms, Humans, Lung Neoplasms, Male, Middle Aged, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Rad52 DNA Repair and Recombination Protein, Risk Factors, Journal Article, Research Support, N.I.H., Extramural",

author = "Manon Delahaye-Sourdeix and Javier Oliver and Timofeeva, {Maria N} and Val{\'e}rie Gaborieau and Mattias Johansson and Am{\'e}lie Chabrier and Wozniak, {Magdalena B} and Brenner, {Darren R} and Vall{\'e}e, {Maxime P} and Devasena Anantharaman and Pagona Lagiou and Ivana Holc{\'a}tov{\'a} and Lorenzo Richiardi and Kristina Kjaerheim and Antonio Agudo and Xavier Castellsagu{\'e} and Macfarlane, {Tatiana V} and Luigi Barzan and Cristina Canova and Thakker, {Nalin S} and Conway, {David I} and Ariana Znaor and Healy, {Claire M} and Wolfgang Ahrens and David Zaridze and Neonilia Szeszenia-Dabrowska and Jolanta Lissowska and Eleonora Fabianova and Mates, {Ioan Nicolae} and Vladimir Bencko and Lenka Foretova and Vladimir Janout and Curado, {Maria Paula} and Sergio Koifman and Ana Menezes and Victor W{\"u}nsch-Filho and Jos{\'e} Eluf-Neto and Paolo Boffetta and Garrote, {Leticia Fern{\'a}ndez} and Diego Serraino and Marcin Lener and Ewa Jaworowska and Jan Lubi{\'n}ski and Stefania Boccia and Thangarajan Rajkumar and Samant, {Tanuja A} and Mahimkar, {Manoj B} and Keitaro Matsuo and Silvia Franceschi and Graham Byrnes and Paul Brennan and McKay, {James D}",

note = "US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116)",

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Delahaye-Sourdeix, M, Oliver, J, Timofeeva, MN, Gaborieau, V, Johansson, M, Chabrier, A, Wozniak, MB, Brenner, DR, Vallée, MP, Anantharaman, D, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, TV, Barzan, L, Canova, C, Thakker, NS, Conway, DI, Znaor, A, Healy, CM, Ahrens, W, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Fabianova, E, Mates, IN, Bencko, V, Foretova, L, Janout, V, Curado, MP, Koifman, S, Menezes, A, Wünsch-Filho, V, Eluf-Neto, J, Boffetta, P, Garrote, LF, Serraino, D, Lener, M, Jaworowska, E, Lubiński, J, Boccia, S, Rajkumar, T, Samant, TA, Mahimkar, MB, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P & McKay, JD 2015, 'The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract', PLoS ONE, vol. 10, no. 3, pp. e0117639. https://doi.org/10.1371/journal.pone.0117639

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

N1 - US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116)

PY - 2015/3/20

Y1 - 2015/3/20

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 - Carcinoma, Squamous Cell

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 12

KW - Computer Simulation

KW - Demography

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Germ Cells

KW - Head and Neck Neoplasms

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Physical Chromosome Mapping

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Rad52 DNA Repair and Recombination Protein

KW - Risk Factors

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1371/journal.pone.0117639

DO - 10.1371/journal.pone.0117639

M3 - Article

C2 - 25793373

SN - 1932-6203

VL - 10

SP - e0117639

JO - PLoS ONE

JF - PLoS ONE

IS - 3

ER -

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Abstract

Keywords

UN SDGs

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