30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes
It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2...
Gespeichert in:
| Veröffentlicht in: | European journal of human genetics : EJHG 2022-04, Vol.30 (4), p.413-419 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 419 |
|---|---|
| container_issue | 4 |
| container_start_page | 413 |
| container_title | European journal of human genetics : EJHG |
| container_volume | 30 |
| creator | Woodward, Emma R Green, Kate Burghel, George J Bulman, Michael Clancy, Tara Lalloo, Fiona Schlecht, Helene Wallace, Andrew J Evans, D Gareth |
| description | It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies. |
| doi_str_mv | 10.1038/s41431-021-01011-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8645350</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2647963400</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-4853538944da983a4fd1a7106d52673453c7724b02f0263f0dc66f259b0f68003</originalsourceid><addsrcrecordid>eNpdkc2KFDEUhQtRnHH0BVxIwI2b0pu6qVRqI8jgHwy40XVIJzfdGauTMqmSmZfwmU13j4O6CAnc75zcw2ma5xxec0D1pggukLfQ1cOB81Y9aM65GGTbC1QP6xu4aoXieNY8KeUaoA4H_rg5Q6Gk5CjPm18I7JZMZnQzUw4ULbHkWYiObpg1hVhwFJfggzVLSJGZ6FhaF5v2VA5kZaxxxBYqS4jbqmS7sN21OZTvbJPJlOWosWlKmexipiqpv2Q2Z3KhzKmEo_GWIpWnzSNvpkLP7u6L5tuH918vP7VXXz5-vnx31VqBsNRMPfaoRiGcGRUa4R03Awfp-k4OKHq0w9CJDXQeOokenJXSd_24AS8VAF40b0--87rZk7M1YjaTnnPYm3yrkwn630kMO71NP7WS1bw_GLy6M8jpx1qz630olqbJREpr0Z2EATnHkVf05X_odVpzrPEqJYZRojhu1J0om1Mpmfz9Mhz0oW59qlvXuvWxbq2q6MXfMe4lf_rF37UppxM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2647963400</pqid></control><display><type>article</type><title>30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Woodward, Emma R ; Green, Kate ; Burghel, George J ; Bulman, Michael ; Clancy, Tara ; Lalloo, Fiona ; Schlecht, Helene ; Wallace, Andrew J ; Evans, D Gareth</creator><creatorcontrib>Woodward, Emma R ; Green, Kate ; Burghel, George J ; Bulman, Michael ; Clancy, Tara ; Lalloo, Fiona ; Schlecht, Helene ; Wallace, Andrew J ; Evans, D Gareth</creatorcontrib><description>It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.</description><identifier>ISSN: 1018-4813</identifier><identifier>EISSN: 1476-5438</identifier><identifier>DOI: 10.1038/s41431-021-01011-8</identifier><identifier>PMID: 34866136</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adenomatous polyposis coli ; BRCA1 protein ; BRCA2 protein ; Breast cancer ; Cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Disease prevention ; DNA Mismatch Repair - genetics ; E-cadherin ; Genes, BRCA2 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Mismatch repair ; MLH1 protein ; MSH2 protein ; MSH6 protein ; p53 Protein ; PTEN protein ; Smad4 protein</subject><ispartof>European journal of human genetics : EJHG, 2022-04, Vol.30 (4), p.413-419</ispartof><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-4853538944da983a4fd1a7106d52673453c7724b02f0263f0dc66f259b0f68003</citedby><cites>FETCH-LOGICAL-c430t-4853538944da983a4fd1a7106d52673453c7724b02f0263f0dc66f259b0f68003</cites><orcidid>0000-0002-6297-2855 ; 0000-0002-8482-5784</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645350/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645350/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34866136$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Woodward, Emma R</creatorcontrib><creatorcontrib>Green, Kate</creatorcontrib><creatorcontrib>Burghel, George J</creatorcontrib><creatorcontrib>Bulman, Michael</creatorcontrib><creatorcontrib>Clancy, Tara</creatorcontrib><creatorcontrib>Lalloo, Fiona</creatorcontrib><creatorcontrib>Schlecht, Helene</creatorcontrib><creatorcontrib>Wallace, Andrew J</creatorcontrib><creatorcontrib>Evans, D Gareth</creatorcontrib><title>30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes</title><title>European journal of human genetics : EJHG</title><addtitle>Eur J Hum Genet</addtitle><description>It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.</description><subject>Adenomatous polyposis coli</subject><subject>BRCA1 protein</subject><subject>BRCA2 protein</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>Disease prevention</subject><subject>DNA Mismatch Repair - genetics</subject><subject>E-cadherin</subject><subject>Genes, BRCA2</subject><subject>Genetic Predisposition to Disease</subject><subject>Germ-Line Mutation</subject><subject>Humans</subject><subject>Mismatch repair</subject><subject>MLH1 protein</subject><subject>MSH2 protein</subject><subject>MSH6 protein</subject><subject>p53 Protein</subject><subject>PTEN protein</subject><subject>Smad4 protein</subject><issn>1018-4813</issn><issn>1476-5438</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</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><recordid>eNpdkc2KFDEUhQtRnHH0BVxIwI2b0pu6qVRqI8jgHwy40XVIJzfdGauTMqmSmZfwmU13j4O6CAnc75zcw2ma5xxec0D1pggukLfQ1cOB81Y9aM65GGTbC1QP6xu4aoXieNY8KeUaoA4H_rg5Q6Gk5CjPm18I7JZMZnQzUw4ULbHkWYiObpg1hVhwFJfggzVLSJGZ6FhaF5v2VA5kZaxxxBYqS4jbqmS7sN21OZTvbJPJlOWosWlKmexipiqpv2Q2Z3KhzKmEo_GWIpWnzSNvpkLP7u6L5tuH918vP7VXXz5-vnx31VqBsNRMPfaoRiGcGRUa4R03Awfp-k4OKHq0w9CJDXQeOokenJXSd_24AS8VAF40b0--87rZk7M1YjaTnnPYm3yrkwn630kMO71NP7WS1bw_GLy6M8jpx1qz630olqbJREpr0Z2EATnHkVf05X_odVpzrPEqJYZRojhu1J0om1Mpmfz9Mhz0oW59qlvXuvWxbq2q6MXfMe4lf_rF37UppxM</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Woodward, Emma R</creator><creator>Green, Kate</creator><creator>Burghel, George J</creator><creator>Bulman, Michael</creator><creator>Clancy, Tara</creator><creator>Lalloo, Fiona</creator><creator>Schlecht, Helene</creator><creator>Wallace, Andrew J</creator><creator>Evans, D Gareth</creator><general>Nature Publishing Group</general><general>Springer International Publishing</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6297-2855</orcidid><orcidid>https://orcid.org/0000-0002-8482-5784</orcidid></search><sort><creationdate>20220401</creationdate><title>30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes</title><author>Woodward, Emma R ; Green, Kate ; Burghel, George J ; Bulman, Michael ; Clancy, Tara ; Lalloo, Fiona ; Schlecht, Helene ; Wallace, Andrew J ; Evans, D Gareth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-4853538944da983a4fd1a7106d52673453c7724b02f0263f0dc66f259b0f68003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adenomatous polyposis coli</topic><topic>BRCA1 protein</topic><topic>BRCA2 protein</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>Disease prevention</topic><topic>DNA Mismatch Repair - genetics</topic><topic>E-cadherin</topic><topic>Genes, BRCA2</topic><topic>Genetic Predisposition to Disease</topic><topic>Germ-Line Mutation</topic><topic>Humans</topic><topic>Mismatch repair</topic><topic>MLH1 protein</topic><topic>MSH2 protein</topic><topic>MSH6 protein</topic><topic>p53 Protein</topic><topic>PTEN protein</topic><topic>Smad4 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Woodward, Emma R</creatorcontrib><creatorcontrib>Green, Kate</creatorcontrib><creatorcontrib>Burghel, George J</creatorcontrib><creatorcontrib>Bulman, Michael</creatorcontrib><creatorcontrib>Clancy, Tara</creatorcontrib><creatorcontrib>Lalloo, Fiona</creatorcontrib><creatorcontrib>Schlecht, Helene</creatorcontrib><creatorcontrib>Wallace, Andrew J</creatorcontrib><creatorcontrib>Evans, D Gareth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of human genetics : EJHG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Woodward, Emma R</au><au>Green, Kate</au><au>Burghel, George J</au><au>Bulman, Michael</au><au>Clancy, Tara</au><au>Lalloo, Fiona</au><au>Schlecht, Helene</au><au>Wallace, Andrew J</au><au>Evans, D Gareth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes</atitle><jtitle>European journal of human genetics : EJHG</jtitle><addtitle>Eur J Hum Genet</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>30</volume><issue>4</issue><spage>413</spage><epage>419</epage><pages>413-419</pages><issn>1018-4813</issn><eissn>1476-5438</eissn><abstract>It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>34866136</pmid><doi>10.1038/s41431-021-01011-8</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-6297-2855</orcidid><orcidid>https://orcid.org/0000-0002-8482-5784</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1018-4813 |
| ispartof | European journal of human genetics : EJHG, 2022-04, Vol.30 (4), p.413-419 |
| issn | 1018-4813 1476-5438 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8645350 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Adenomatous polyposis coli BRCA1 protein BRCA2 protein Breast cancer Cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Disease prevention DNA Mismatch Repair - genetics E-cadherin Genes, BRCA2 Genetic Predisposition to Disease Germ-Line Mutation Humans Mismatch repair MLH1 protein MSH2 protein MSH6 protein p53 Protein PTEN protein Smad4 protein |
| title | 30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T20%3A08%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=30%20year%20experience%20of%20index%20case%20identification%20and%20outcomes%20of%20cascade%20testing%20in%20high-risk%20breast%20and%20colorectal%20cancer%20predisposition%20genes&rft.jtitle=European%20journal%20of%20human%20genetics%20:%20EJHG&rft.au=Woodward,%20Emma%20R&rft.date=2022-04-01&rft.volume=30&rft.issue=4&rft.spage=413&rft.epage=419&rft.pages=413-419&rft.issn=1018-4813&rft.eissn=1476-5438&rft_id=info:doi/10.1038/s41431-021-01011-8&rft_dat=%3Cproquest_pubme%3E2647963400%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2647963400&rft_id=info:pmid/34866136&rfr_iscdi=true |