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. 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

Stony Brook University

International Agency for Research on Cancer
University of Edinburgh
National and Kapodistrian University of Athens
Charles University
University of Turin
Cancer Registry of Norway Institute of Population-Based Cancer Research
Bellvitge Biomedical Research Institute
CIBER Epidemiología y Salud Pública (CIBERESP)
University of Aberdeen
General Hospital of Pordenone
University of Padua
Imperial College London
University of Manchester
University of Glasgow
Croatian National Institute of Public Health
Trinity College Dublin
Leibniz Institute for Prevention Research and Epidemiology
University of Bremen
Blokhin Cancer Research Center
Nofer Institute of Occupational Medicine
Maria Sklodowska-Curie Institute of Oncology
Regional Authority of Public Health
Carol Davila University of Medicine and Pharmacy
Masaryk Memorial Cancer Institute
Palacký University Olomouc
University of Strathclyde
Fundação Oswaldo Cruz
Universidade Federal de Pelotas
Universidade de São Paulo
National School of Public Health
IRCCS Centro di Riferimento Oncologico - Aviano PN
Pomeranian Medical University in Szczecin
Catholic University of the Sacred Heart
Cancer Institute India
Advanced Centre for Treatment Research and Education in Cancer
Kyushu Dental College

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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
Article number	e0117639
Journal	PLoS ONE
Volume	10
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0117639
State	Published - Mar 20 2015

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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), Article e0117639. https://doi.org/10.1371/journal.pone.0117639

@article{a973c80a1bc74911add735a5f3116da3,

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.",

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 = "Publisher Copyright: {\textcopyright} 2015 Delahaye-Sourdeix et al.",

year = "2015",

month = mar,

day = "20",

doi = "10.1371/journal.pone.0117639",

language = "English",

volume = "10",

journal = "PLoS ONE",

issn = "1932-6203",

number = "3",

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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, 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.

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.

UR - https://www.scopus.com/pages/publications/84925955087

U2 - 10.1371/journal.pone.0117639

DO - 10.1371/journal.pone.0117639

M3 - Article

C2 - 25793373

SN - 1932-6203

VL - 10

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e0117639

ER -

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

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