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.
authors: Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Manon
authors: M
authors: Delahaye-Sourdeix
authors: Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Javier
authors: J
authors: Oliver
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France; Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, United Kingdom.
authors: Maria N
authors: MN
authors: Timofeeva
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Valérie
authors: V
authors: Gaborieau
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Mattias
authors: M
authors: Johansson
authors: Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Amélie
authors: A
authors: Chabrier
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Magdalena B
authors: MB
authors: Wozniak
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Darren R
authors: DR
authors: Brenner
authors: Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Maxime P
authors: MP
authors: Vallée
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Devasena
authors: D
authors: Anantharaman
authors: Department of Hygiene, Epidemiology and Medical Statistics, University of Athens School of Medicine, Athens, Greece.
authors: Pagona
authors: P
authors: Lagiou
authors: Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Ivana
authors: I
authors: Holcátová
authors: University of Turin, Department of Medical Sciences, Unit of Cancer Epidemiology, Turin, Italy.
authors: Lorenzo
authors: L
authors: Richiardi
authors: Cancer Registry of Norway, Oslo, Norway.
authors: Kristina
authors: K
authors: Kjaerheim
authors: Catalan Institute of Oncology-ICO, IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain.
authors: Antonio
authors: A
authors: Agudo
authors: Catalan Institute of Oncology-ICO, IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors: Xavier
authors: X
authors: Castellsagué
authors: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
authors: Tatiana V
authors: TV
authors: Macfarlane
authors: General Hospital of Pordenone, Pordenone, Italy.
authors: Luigi
authors: L
authors: Barzan
authors: Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy; MRC-HPA Centre for Environment and Health, Respiratory Epidemiology and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors: Cristina
authors: C
authors: Canova
authors: University of Manchester, School of Dentistry, Manchester, United Kingdom.
authors: Nalin S
authors: NS
authors: Thakker
authors: University of Glasgow Dental School, Glasgow, Scotland, United Kingdom.
authors: David I
authors: DI
authors: Conway
authors: Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia.
authors: Ariana
authors: A
authors: Znaor
authors: Trinity College School of Dental Science, Dublin, Ireland.
authors: Claire M
authors: CM
authors: Healy
authors: Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany; Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany.
authors: Wolfgang
authors: W
authors: Ahrens
authors: Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russian Federation.
authors: David
authors: D
authors: Zaridze
authors: Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland.
authors: Neonilia
authors: N
authors: Szeszenia-Dabrowska
authors: Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors: Jolanta
authors: J
authors: Lissowska
authors: Regional Authority of Public Health, Banska Bystrica, Slovakia.
authors: Eleonora
authors: E
authors: Fabianova
authors: Saint Mary General and Esophageal Surgery Clinic, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors: Ioan Nicolae
authors: IN
authors: Mates
authors: Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Vladimir
authors: V
authors: Bencko
authors: Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Masaryk University, Brno, Czech Republic.
authors: Lenka
authors: L
authors: Foretova
authors: Palacky University, Olomouc, Czech Republic.
authors: Vladimir
authors: V
authors: Janout
authors: International Prevention Research Institute (IPRI), Ecully, France.
authors: Maria Paula
authors: MP
authors: Curado
authors: National School of Public Health/FIOCRUZ, Rio de Janeiro, Brazil.
authors: Sergio
authors: S
authors: Koifman
authors: Universidade Federal de Pelotas, Pelotas, Brazil.
authors: Ana
authors: A
authors: Menezes
authors: Universidade de Sao Paulo, Sao Paulo, Brazil.
authors: Victor
authors: V
authors: Wünsch-Filho
authors: Universidade de Sao Paulo, Sao Paulo, Brazil.
authors: José
authors: J
authors: Eluf-Neto
authors: The Tisch Cancer Institute Mount Sinai School of Medicine, New York, NY, United States of America.
authors: Paolo
authors: P
authors: Boffetta
authors: Institute of Oncology and Radiobiology, Havana, Cuba.
authors: Leticia Fernández
authors: LF
authors: Garrote
authors: Centro di Riferimento Oncologico, IRCSS, Unit of Epidemiology and Biostatistics, Aviano, Italy.
authors: Diego
authors: D
authors: Serraino
authors: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors: Marcin
authors: M
authors: Lener
authors: Department of Otolaryngology and Laryngological Oncology, Pomeranian Medical University, Szczecin, Poland.
authors: Ewa
authors: E
authors: Jaworowska
authors: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors: Jan
authors: J
authors: Lubiński
authors: Institute of Public Health, Section of Hygiene, Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Stefania
authors: S
authors: Boccia
authors: Dept. of Molecular Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India.
authors: Thangarajan
authors: T
authors: Rajkumar
authors: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
authors: Tanuja A
authors: TA
authors: Samant
authors: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
authors: Manoj B
authors: MB
authors: Mahimkar
authors: Department of Health Promotion, Division of Oral Pathology, Kyushu Dental University, Kitakyushu, Japan.
authors: Keitaro
authors: K
authors: Matsuo
authors: Infections and Cancer Epidemiology group (ICE), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Silvia
authors: S
authors: Franceschi
authors: Biostatistics group (BST), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Graham
authors: G
authors: Byrnes
authors: Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
authors: Paul
authors: P
authors: Brennan
authors: Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
authors: James D
authors: JD
authors: McKay
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003198:Computer Simulation; D003710:Demography; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005854:Germ Cells; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*; D012307:Risk Factors
chemical_list: C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein