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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968735/ https://www.ncbi.nlm.nih.gov/pubmed/33667223 http://dx.doi.org/10.1371/journal.pgen.1009254 |
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author | Lesseur, Corina Ferreiro-Iglesias, Aida McKay, James D. Bossé, Yohan Johansson, Mattias Gaborieau, Valerie Landi, Maria Teresa Christiani, David C. Caporaso, Neil C. Bojesen, Stig E. Amos, Christopher I. Shete, Sanjay Liu, Geoffrey Rennert, Gadi Albanes, Demetrius Aldrich, Melinda C. Tardon, Adonina Chen, Chu Triantafillos, Liloglou Field, John K. Teare, Marion Dawn Kiemeney, Lambertus A. Diergaarde, Brenda Ferris, Robert L. Zienolddiny, Shanbeh Lam, Stephen Olshan, Andrew F. Weissler, Mark C. Lacko, Martin Risch, Angela Bickeböller, Heike Ness, Andy R. Thomas, Steve Le Marchand, Loic Schabath, Matthew B. Wünsch-Filho, Victor Tajara, Eloiza H. Andrew, Angeline S. Clifford, Gary M. Lazarus, Philip Grankvist, Kjell Johansson, Mikael Arnold, Susanne Melander, Olle Brunnström, Hans Boccia, Stefania Cadoni, Gabriella Timens, Wim Obeidat, Ma’en Xiao, Xiangjun Houlston, Richard S. Hung, Rayjean J. Brennan, Paul |
author_facet | Lesseur, Corina Ferreiro-Iglesias, Aida McKay, James D. Bossé, Yohan Johansson, Mattias Gaborieau, Valerie Landi, Maria Teresa Christiani, David C. Caporaso, Neil C. Bojesen, Stig E. Amos, Christopher I. Shete, Sanjay Liu, Geoffrey Rennert, Gadi Albanes, Demetrius Aldrich, Melinda C. Tardon, Adonina Chen, Chu Triantafillos, Liloglou Field, John K. Teare, Marion Dawn Kiemeney, Lambertus A. Diergaarde, Brenda Ferris, Robert L. Zienolddiny, Shanbeh Lam, Stephen Olshan, Andrew F. Weissler, Mark C. Lacko, Martin Risch, Angela Bickeböller, Heike Ness, Andy R. Thomas, Steve Le Marchand, Loic Schabath, Matthew B. Wünsch-Filho, Victor Tajara, Eloiza H. Andrew, Angeline S. Clifford, Gary M. Lazarus, Philip Grankvist, Kjell Johansson, Mikael Arnold, Susanne Melander, Olle Brunnström, Hans Boccia, Stefania Cadoni, Gabriella Timens, Wim Obeidat, Ma’en Xiao, Xiangjun Houlston, Richard S. Hung, Rayjean J. Brennan, Paul |
author_sort | Lesseur, Corina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7968735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79687352021-03-31 Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers Lesseur, Corina Ferreiro-Iglesias, Aida McKay, James D. Bossé, Yohan Johansson, Mattias Gaborieau, Valerie Landi, Maria Teresa Christiani, David C. Caporaso, Neil C. Bojesen, Stig E. Amos, Christopher I. Shete, Sanjay Liu, Geoffrey Rennert, Gadi Albanes, Demetrius Aldrich, Melinda C. Tardon, Adonina Chen, Chu Triantafillos, Liloglou Field, John K. Teare, Marion Dawn Kiemeney, Lambertus A. Diergaarde, Brenda Ferris, Robert L. Zienolddiny, Shanbeh Lam, Stephen Olshan, Andrew F. Weissler, Mark C. Lacko, Martin Risch, Angela Bickeböller, Heike Ness, Andy R. Thomas, Steve Le Marchand, Loic Schabath, Matthew B. Wünsch-Filho, Victor Tajara, Eloiza H. Andrew, Angeline S. Clifford, Gary M. Lazarus, Philip Grankvist, Kjell Johansson, Mikael Arnold, Susanne Melander, Olle Brunnström, Hans Boccia, Stefania Cadoni, Gabriella Timens, Wim Obeidat, Ma’en Xiao, Xiangjun Houlston, Richard S. Hung, Rayjean J. Brennan, Paul PLoS Genet Research Article 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. Public Library of Science 2021-03-05 /pmc/articles/PMC7968735/ /pubmed/33667223 http://dx.doi.org/10.1371/journal.pgen.1009254 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Lesseur, Corina Ferreiro-Iglesias, Aida McKay, James D. Bossé, Yohan Johansson, Mattias Gaborieau, Valerie Landi, Maria Teresa Christiani, David C. Caporaso, Neil C. Bojesen, Stig E. Amos, Christopher I. Shete, Sanjay Liu, Geoffrey Rennert, Gadi Albanes, Demetrius Aldrich, Melinda C. Tardon, Adonina Chen, Chu Triantafillos, Liloglou Field, John K. Teare, Marion Dawn Kiemeney, Lambertus A. Diergaarde, Brenda Ferris, Robert L. Zienolddiny, Shanbeh Lam, Stephen Olshan, Andrew F. Weissler, Mark C. Lacko, Martin Risch, Angela Bickeböller, Heike Ness, Andy R. Thomas, Steve Le Marchand, Loic Schabath, Matthew B. Wünsch-Filho, Victor Tajara, Eloiza H. Andrew, Angeline S. Clifford, Gary M. Lazarus, Philip Grankvist, Kjell Johansson, Mikael Arnold, Susanne Melander, Olle Brunnström, Hans Boccia, Stefania Cadoni, Gabriella Timens, Wim Obeidat, Ma’en Xiao, Xiangjun Houlston, Richard S. Hung, Rayjean J. Brennan, Paul Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title_full | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title_fullStr | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title_full_unstemmed | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title_short | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
title_sort | genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968735/ https://www.ncbi.nlm.nih.gov/pubmed/33667223 http://dx.doi.org/10.1371/journal.pgen.1009254 |
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