An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid cancer susceptibility
Papillary Thyroid Cancer (PTC) is a heterogeneous and complex disease; susceptibility to PTC is influenced by the joint effects of multiple common, low-penetrance genes, although relatively few have been identified to date. Here we applied a rigorous combined approach to assess both the individual a...
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| creator | Landa, Iñigo Boullosa, Cesar Inglada-Pérez, Lucía Sastre-Perona, Ana Pastor, Susana Velázquez, Antonia Mancikova, Veronika Ruiz-Llorente, Sergio Schiavi, Francesca Marcos, Ricard Malats, Nuria Opocher, Giuseppe Diaz-Uriarte, Ramon Santisteban, Pilar Valencia, Alfonso Robledo, Mercedes |
| description | Papillary Thyroid Cancer (PTC) is a heterogeneous and complex disease; susceptibility to PTC is influenced by the joint effects of multiple common, low-penetrance genes, although relatively few have been identified to date. Here we applied a rigorous combined approach to assess both the individual and epistatic contributions of genetic factors to PTC susceptibility, based on one of the largest series of thyroid cancer cases described to date. In addition to identifying the involvement of TSHR variation in classic PTC, our pioneer study of epistasis revealed a significant interaction between variants in STK17B and PAX8. The interaction was detected by MD-MBR (p = 0.00010) and confirmed by other methods, and then replicated in a second independent series of patients (MD-MBR p = 0.017). Furthermore, we demonstrated an inverse correlation between expression of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas. Overall, our work sheds additional light on the genetic basis of thyroid cancer susceptibility, and suggests a new direction for the exploration of the inherited genetic contribution to disease using association studies. |
| doi_str_mv | 10.1371/journal.pone.0074765 |
| format | Article |
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Here we applied a rigorous combined approach to assess both the individual and epistatic contributions of genetic factors to PTC susceptibility, based on one of the largest series of thyroid cancer cases described to date. In addition to identifying the involvement of TSHR variation in classic PTC, our pioneer study of epistasis revealed a significant interaction between variants in STK17B and PAX8. The interaction was detected by MD-MBR (p = 0.00010) and confirmed by other methods, and then replicated in a second independent series of patients (MD-MBR p = 0.017). Furthermore, we demonstrated an inverse correlation between expression of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas. Overall, our work sheds additional light on the genetic basis of thyroid cancer susceptibility, and suggests a new direction for the exploration of the inherited genetic contribution to disease using association studies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0074765</identifier><identifier>PMID: 24086368</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis Regulatory Proteins - genetics ; Bioinformatics ; Biology ; Breast cancer ; Cancer ; Cancer genetics ; Carcinoma - genetics ; Carcinoma, Papillary ; Cell Line, Tumor ; Cell lines ; Deoxyribonucleic acid ; Disease susceptibility ; DNA ; Epistasis ; Epistasis, Genetic ; Female ; Forkhead Transcription Factors - genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genes ; Genetic aspects ; Genetic factors ; Genetic Predisposition to Disease ; Genetic research ; Genomes ; Genomics ; Humans ; Laboratories ; Male ; Medical research ; Middle Aged ; Models, Genetic ; Oncology ; Paired Box Transcription Factors - genetics ; Papillary thyroid cancer ; Pathogenesis ; Pax8 protein ; PAX8 Transcription Factor ; Polymorphism, Single Nucleotide - genetics ; Protein-Serine-Threonine Kinases - genetics ; Reproducibility of Results ; Risk Factors ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Studies ; Thyroid ; Thyroid cancer ; Thyroid Cancer, Papillary ; Thyroid carcinoma ; Thyroid Neoplasms - genetics ; Thyroid-stimulating hormone receptors</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e74765-e74765</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Landa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Landa et al 2013 Landa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f4294502cc3ff018b77a8fe806bf450cb6aa869cf059f94acc66934bd17923303</citedby><cites>FETCH-LOGICAL-c692t-f4294502cc3ff018b77a8fe806bf450cb6aa869cf059f94acc66934bd17923303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781145/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781145/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24086368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Miao, Xiaoping</contributor><creatorcontrib>Landa, Iñigo</creatorcontrib><creatorcontrib>Boullosa, Cesar</creatorcontrib><creatorcontrib>Inglada-Pérez, Lucía</creatorcontrib><creatorcontrib>Sastre-Perona, Ana</creatorcontrib><creatorcontrib>Pastor, Susana</creatorcontrib><creatorcontrib>Velázquez, Antonia</creatorcontrib><creatorcontrib>Mancikova, Veronika</creatorcontrib><creatorcontrib>Ruiz-Llorente, Sergio</creatorcontrib><creatorcontrib>Schiavi, Francesca</creatorcontrib><creatorcontrib>Marcos, Ricard</creatorcontrib><creatorcontrib>Malats, Nuria</creatorcontrib><creatorcontrib>Opocher, Giuseppe</creatorcontrib><creatorcontrib>Diaz-Uriarte, Ramon</creatorcontrib><creatorcontrib>Santisteban, Pilar</creatorcontrib><creatorcontrib>Valencia, Alfonso</creatorcontrib><creatorcontrib>Robledo, Mercedes</creatorcontrib><title>An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid cancer susceptibility</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Papillary Thyroid Cancer (PTC) is a heterogeneous and complex disease; susceptibility to PTC is influenced by the joint effects of multiple common, low-penetrance genes, although relatively few have been identified to date. 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genetics</subject><subject>Papillary thyroid cancer</subject><subject>Pathogenesis</subject><subject>Pax8 protein</subject><subject>PAX8 Transcription Factor</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Reproducibility of Results</subject><subject>Risk Factors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Studies</subject><subject>Thyroid</subject><subject>Thyroid cancer</subject><subject>Thyroid Cancer, Papillary</subject><subject>Thyroid carcinoma</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid-stimulating hormone receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQkJw2MWOHTu-VFoqPlZUKqIFcbMcZ7LrKmsH2wH23-Nl02qDekA5JBo_8874zUyWPcVojgnHb67d4K3q5r2zMEeIU87Ke9kxFqSYsQKR-wffR9mjEK4RKknF2MPsqKCoYoRVxxksbA69CVFFo3NjI3ilo3E2ryH-ArB5XEP-efG9ypVt8surT5i_zVdgISQ671Vvuk75bcK23pkm18pq8HkYgoY-mtp0Jm4fZw9a1QV4Mr5Psq_v312dfZydX3xYni3OZ5qJIs5aWghaokJr0rYIVzXnqmqhQqxuU1zXTKmKCd2iUrSCKq0ZE4TWDeaiIASRk-z5XrfvXJCjQ0FiSkpKMGY8Ecs90Th1LXtvNql56ZSRfwPOr6TyyYoOJNW4ZViUmhBMNdGi4akpyglrsNYVJK3TsdpQb6DRYKNX3UR0emLNWq7cT0l4hTEtk8CrUcC7HwOEKDcm2ZYMteCGXd-UEMELxhL64h_07tuN1EqlCxjbulRX70TlgqaipOBCJGp-B5WeBjZGp3FqTYpPEl5PEhIT4XdcqSEEubz88v_sxbcp-_KAXYPq4jq4btjNX5iCdA9q70Lw0N6ajJHcbcONG3K3DXLchpT27PAH3SbdjD_5AwkfA-s</recordid><startdate>20130923</startdate><enddate>20130923</enddate><creator>Landa, Iñigo</creator><creator>Boullosa, Cesar</creator><creator>Inglada-Pérez, Lucía</creator><creator>Sastre-Perona, Ana</creator><creator>Pastor, Susana</creator><creator>Velázquez, Antonia</creator><creator>Mancikova, Veronika</creator><creator>Ruiz-Llorente, Sergio</creator><creator>Schiavi, Francesca</creator><creator>Marcos, Ricard</creator><creator>Malats, Nuria</creator><creator>Opocher, Giuseppe</creator><creator>Diaz-Uriarte, Ramon</creator><creator>Santisteban, Pilar</creator><creator>Valencia, Alfonso</creator><creator>Robledo, Mercedes</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130923</creationdate><title>An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid cancer susceptibility</title><author>Landa, Iñigo ; Boullosa, Cesar ; Inglada-Pérez, Lucía ; Sastre-Perona, Ana ; Pastor, Susana ; Velázquez, Antonia ; Mancikova, Veronika ; Ruiz-Llorente, Sergio ; Schiavi, Francesca ; Marcos, Ricard ; Malats, Nuria ; Opocher, Giuseppe ; Diaz-Uriarte, Ramon ; Santisteban, Pilar ; Valencia, Alfonso ; Robledo, Mercedes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f4294502cc3ff018b77a8fe806bf450cb6aa869cf059f94acc66934bd17923303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis Regulatory Proteins - 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Here we applied a rigorous combined approach to assess both the individual and epistatic contributions of genetic factors to PTC susceptibility, based on one of the largest series of thyroid cancer cases described to date. In addition to identifying the involvement of TSHR variation in classic PTC, our pioneer study of epistasis revealed a significant interaction between variants in STK17B and PAX8. The interaction was detected by MD-MBR (p = 0.00010) and confirmed by other methods, and then replicated in a second independent series of patients (MD-MBR p = 0.017). Furthermore, we demonstrated an inverse correlation between expression of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas. 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| language | eng |
| recordid | cdi_plos_journals_1435431167 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Apoptosis Regulatory Proteins - genetics Bioinformatics Biology Breast cancer Cancer Cancer genetics Carcinoma - genetics Carcinoma, Papillary Cell Line, Tumor Cell lines Deoxyribonucleic acid Disease susceptibility DNA Epistasis Epistasis, Genetic Female Forkhead Transcription Factors - genetics Gene Expression Regulation, Neoplastic Gene Silencing Genes Genetic aspects Genetic factors Genetic Predisposition to Disease Genetic research Genomes Genomics Humans Laboratories Male Medical research Middle Aged Models, Genetic Oncology Paired Box Transcription Factors - genetics Papillary thyroid cancer Pathogenesis Pax8 protein PAX8 Transcription Factor Polymorphism, Single Nucleotide - genetics Protein-Serine-Threonine Kinases - genetics Reproducibility of Results Risk Factors RNA, Messenger - genetics RNA, Messenger - metabolism Studies Thyroid Thyroid cancer Thyroid Cancer, Papillary Thyroid carcinoma Thyroid Neoplasms - genetics Thyroid-stimulating hormone receptors |
| title | An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid cancer susceptibility |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T19%3A22%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20epistatic%20interaction%20between%20the%20PAX8%20and%20STK17B%20genes%20in%20papillary%20thyroid%20cancer%20susceptibility&rft.jtitle=PloS%20one&rft.au=Landa,%20I%C3%B1igo&rft.date=2013-09-23&rft.volume=8&rft.issue=9&rft.spage=e74765&rft.epage=e74765&rft.pages=e74765-e74765&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0074765&rft_dat=%3Cgale_plos_%3EA478132799%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1435431167&rft_id=info:pmid/24086368&rft_galeid=A478132799&rft_doaj_id=oai_doaj_org_article_4c1f6195c3314c3c9d7f014736d1cc8e&rfr_iscdi=true |