Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers
Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqC...
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| Published in: | PLoS genetics Vol. 17; no. 3; p. e1009254 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Public Library of Science
05.03.2021
Public Library of Science (PLoS) |
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| ISSN: | 1553-7404, 1553-7390, 1553-7404 |
| Online Access: | Get full text |
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| Abstract | Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (
P
meta
<5x10
-8
) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285,
TMEM273
). Additionally, three previously unknown loci reached suggestive significance (
P
meta
<5x10
-7
): 1q32.1 (rs12133735, near
MDM4
), 5q31.2 (rs13181561,
TMEM173
) and 19p13.11 (rs61494113,
ABHD8)
. Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (
ADH1B
), 6p21.33 (
STK19
), 6p21.32 (
HLA-DQB1
), 9p21.33 (
CDKN2B-AS1
) and 13q13.1(
BRCA2
). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. |
|---|---|
| AbstractList | Introduction The squamous cell carcinomas (SqCC) of the aerodigestive tract [1], lung squamous cell carcinoma (LuSqCC) and head and neck cancers (HNC, >90% SqCCs) including; oral/pharyngeal SqCC (OSqCC), larynx SqCC (LaSqCC), and esophageal SqCC (ESqCC); are strongly associated with common risk factors such as tobacco smoking, alcohol consumption and human papilloma virus (HPV) infection [2]. [...]recent molecular characterization studies across anatomically distinct SqCCs have shown that histology is more important than tissue of origin in defining tumor molecular profiles determined by shared features including somatic mutations, copy number alternations, deregulation of DNA methylation and/or gene expression[2–4]. Furthermore, a recent large-scale genome-wide genetic correlation analysis across six solid tumors (breast, colorectal, head/neck, lung, ovary and prostate cancer), highlighted that the strongest genetic correlation was between lung and head and neck cancers [14]. [...]we performed a genome-wide gene-based association analysis (GWGAS) of the SqCC meta-analyses results using MAGMA (Multi-marker Analysis of GenoMic Annotation)[20] (S8 Table). Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Squamous cell carcinomas are specific type of cancer that can arise in multiple organs of the aerodigestive tract including the lung, oral cavity, oropharynx, larynx and esophagus. Previous studies have shown that aerodigestive squamous cell carcinomas share common environmental risk factors (tobacco smoking and alcohol intake). Here, we investigate genetic factors involved in the risk of aerodigestive squamous cell carcinomas as a group in a large genetic association study involving 13,887 cancer cases and 61,961 controls. We identified one genome-wide significant region within 2q33.1 and 3 other suggestive regions at 1q32.1, 5q31.2 and 19p13.11. Gene-based analyses also identify a list of SqCC-related genes that are involved in DNA damage response and epigenetic regulation. Our results suggest some overlap in the genetic factors influencing the risk of aerodigestive squamous cell carcinomas in European populations and highlights the importance of cross-cancer studies. Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (P.sub.meta <5x10.sup.-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (P.sub.meta <5x10.sup.-7 ): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Introduction The squamous cell carcinomas (SqCC) of the aerodigestive tract [1], lung squamous cell carcinoma (LuSqCC) and head and neck cancers (HNC, >90% SqCCs) including; oral/pharyngeal SqCC (OSqCC), larynx SqCC (LaSqCC), and esophageal SqCC (ESqCC); are strongly associated with common risk factors such as tobacco smoking, alcohol consumption and human papilloma virus (HPV) infection [2]. [...]recent molecular characterization studies across anatomically distinct SqCCs have shown that histology is more important than tissue of origin in defining tumor molecular profiles determined by shared features including somatic mutations, copy number alternations, deregulation of DNA methylation and/or gene expression[2–4]. Furthermore, a recent large-scale genome-wide genetic correlation analysis across six solid tumors (breast, colorectal, head/neck, lung, ovary and prostate cancer), highlighted that the strongest genetic correlation was between lung and head and neck cancers [14]. [...]we performed a genome-wide gene-based association analysis (GWGAS) of the SqCC meta-analyses results using MAGMA (Multi-marker Analysis of GenoMic Annotation)[20] (S8 Table). Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant ( P meta <5x10 -8 ) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273 ). Additionally, three previously unknown loci reached suggestive significance ( P meta <5x10 -7 ): 1q32.1 (rs12133735, near MDM4 ), 5q31.2 (rs13181561, TMEM173 ) and 19p13.11 (rs61494113, ABHD8) . Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 ( ADH1B ), 6p21.33 ( STK19 ), 6p21.32 ( HLA-DQB1 ), 9p21.33 ( CDKN2B-AS1 ) and 13q13.1( BRCA2 ). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. |
| Audience | Academic |
| Author | Weissler, Mark C. Chen, Chu Ferreiro-Iglesias, Aida Johansson, Mikael Zienolddiny, Shanbeh Lacko, Martin Andrew, Angeline S. Shete, Sanjay Schabath, Matthew B. Albanes, Demetrius Risch, Angela Gaborieau, Valerie Melander, Olle Lesseur, Corina Teare, Marion Dawn Clifford, Gary M. McKay, James D. Wünsch-Filho, Victor Caporaso, Neil C. Liu, Geoffrey Tardon, Adonina Thomas, Steve Field, John K. Brunnström, Hans Grankvist, Kjell Bossé, Yohan Kiemeney, Lambertus A. Ferris, Robert L. Christiani, David C. Ness, Andy R. Obeidat, Ma’en Bojesen, Stig E. Rennert, Gadi Lam, Stephen Xiao, Xiangjun Lazarus, Philip Boccia, Stefania Diergaarde, Brenda Timens, Wim Houlston, Richard S. Hung, Rayjean J. Arnold, Susanne Tajara, Eloiza H. Johansson, Mattias Amos, Christopher I. Le Marchand, Loic Cadoni, Gabriella Landi, Maria Teresa Bickeböller, Heike Brennan, Paul Olshan, Andrew F. Aldrich, Melinda C. Triantafillos, Liloglou |
| AuthorAffiliation | 22 British Columbia Cancer Agency, Vancouver, Canada 16 School of Health and Related Research, University Of Sheffield, Sheffield, United Kingdom 4 Department of Molecular Medicine, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec City, Canada 2 Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America 35 Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil 40 Department of Radiation Sciences, Umeå University, Umeå, Sweden 46 Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia 36 Biomedical Data Science, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, United States of America 52 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom 19 Graduate Schoo |
| AuthorAffiliation_xml | – name: 7 Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark – name: 22 British Columbia Cancer Agency, Vancouver, Canada – name: 28 Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany – name: 39 Department of Medical Biosciences, Umeå University, Umeå, Sweden – name: 9 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America – name: 14 Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington, United States of America – name: 16 School of Health and Related Research, University Of Sheffield, Sheffield, United Kingdom – name: 43 Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden – name: 30 National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom – name: 35 Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil – name: 10 Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, Canada – name: 32 Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, United States of America – name: 34 Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil – name: 12 Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America – name: 4 Department of Molecular Medicine, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec City, Canada – name: 26 University of Salzburg, Department of Biosciences and Cancer Cluster Salzburg, Salzburg, Austria – name: 11 Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel – name: 42 Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden – name: 46 Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia – name: 41 Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America – name: 29 Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany – name: 45 Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia – name: 6 Department of Environmental Health, Harvard TH Chan School of Public Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America – name: 27 Division of Epigenomics, DKFZ – German Cancer Research Center, Heidelberg, Germany – name: 53 Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada – name: 51 Centre for Heart Lung Innovation, St Paul’s Hospital, The University of British Columbia, Vancouver, Canada – name: NIH, UNITED STATES – name: 8 Department of Medicine, Baylor college of Medicine, Houston, Texas, United States of America – name: 2 Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America – name: 18 Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America – name: 47 Dipartimento Patologia Testa Collo e Organi di Senso, Istituto di Clinica Otorinolaringoiatrica, Università Cattolica del Sacro Cuore, Roma, Italia – name: 21 National Institute of Occupational Health, Oslo, Norway – name: 5 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America – name: 15 Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom – name: 37 Infections Section, Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France – name: 44 Department of Clinical Sciences, Lund University, Lund, Sweden – name: 40 Department of Radiation Sciences, Umeå University, Umeå, Sweden – name: 52 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom – name: 36 Biomedical Data Science, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, United States of America – name: 19 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America – name: 17 Radboud University Medical Center, Nijmegen, The Netherlands – name: 13 Faculty of Medicine, University of Oviedo and CIBERESP, Oviedo, Spain – name: 49 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands – name: 24 Department of Otolaryngology/Head and Neck Surgery, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America – name: 20 UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America – name: 38 Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, United States of America – name: 48 Dipartimento di Scienze dell’Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia – name: 50 GRIAC Research Institute, University of Groningen, Groningen, The Netherlands – name: 23 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America – name: 25 Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands – name: 3 Section of Genetics, Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, World Health Organization, Lyon, France – name: 33 Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America – name: 1 Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France – name: 31 Bristol Dental School, University of Bristol, Bristol, United Kingdom |
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| CorporateAuthor | LUCC: Lunds universitets cancercentrum Övriga starka forskningsmiljöer Section V Patologi, Lund Pathology, Lund Kardiovaskulär forskning - hypertoni Department of Clinical Sciences, Lund Strategiska forskningsområden (SFO) Medicinska fakulteten LUCC: Lund University Cancer Centre Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga Institutionen för kliniska vetenskaper, Lund Profile areas and other strong research environments Lunds universitet Department of Clinical Sciences, Malmö Lund University Sektion V Improved diagnostics and prognostics of lung cancer and metastases to the lungs EpiHealth: Epidemiology for Health Other Strong Research Environments EXODIAB: Excellence of Diabetes Research in Sweden Faculty of Medicine Strategic research areas (SRA) Profilområden och andra starka forskningsmiljöer Cardiovascular Research - Hypertension Institutionen för kliniska vetenskaper, Malmö |
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| Notes | new_version ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 I have read the journal’s policy and the authors of this manuscript have the following competing interests. Dr. Ferris has the following financial disclosures: Aduro Biotech, Inc (consulting); Astra-Zeneca/MedImmune (clinical trial, research funding); Bristol-Myers Squibb (advisory board, clinical trial, research funding); EMD Serono (advisory board); MacroGenics, Inc (advisory board); Merck (advisory board, clinical trial); Novasenta (consulting, stock, research funding); Numab Therapeutics AG (advisory board); Pfizer (advisory board); Sanofi (consultant); Tesaro (research funding) and Zymeworks, Inc (consultant). All other authors have no conflicts to disclose. |
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| Snippet | Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have... Introduction The squamous cell carcinomas (SqCC) of the aerodigestive tract [1], lung squamous cell carcinoma (LuSqCC) and head and neck cancers (HNC, >90%... |
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| SubjectTerms | Alleles Association analysis Biology and Life Sciences Biomarkers, Tumor Breast Cancer and Oncology Cancer och onkologi Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Clinical Medicine Copy number Correlation analysis Datasets Deoxyribonucleic acid Digestive system cancer Digestive System Neoplasms - genetics Digestive System Neoplasms - metabolism Digestive System Neoplasms - pathology DNA DNA methylation Esophageal cancer Esophagus Gene expression Gene loci Genetic analysis Genetic aspects Genetic Loci Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genomic analysis Genotype Head & neck cancer Head and neck cancer Human papillomavirus Humans Klinisk medicin Larynx Lung cancer Lung carcinoma Medical and Health Sciences Medicin och hälsovetenskap Medicine and Health Sciences Meta-analysis Mutation Odds Ratio Ovarian cancer Pharynx Physical Sciences Prostate cancer Research and Analysis Methods Risk factors Signal Transduction Solid tumors Squamous cell carcinoma Tobacco smoking Tumors |
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| Title | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
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