Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer
Abstract It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymo...
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| Veröffentlicht in: | JNCI cancer spectrum 2021-04, Vol.5 (2) |
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| creator | Jenkins, Mark A Buchanan, Daniel D Lai, John Makalic, Enes Dite, Gillian S Win, Aung K Clendenning, Mark Winship, Ingrid M Hayes, Richard B Huyghe, Jeroen R Peters, Ulrike Gallinger, Steven Marchand, Loïc Le Figueiredo, Jane C Pai, Rish K Newcomb, Polly A Church, James M Casey, Graham Hopper, John L |
| description | Abstract
It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer. |
| doi_str_mv | 10.1093/jncics/pkab022 |
| format | Article |
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It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.</description><identifier>ISSN: 2515-5091</identifier><identifier>EISSN: 2515-5091</identifier><identifier>DOI: 10.1093/jncics/pkab022</identifier><identifier>PMID: 33928216</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Brief Communications ; Colorectal Neoplasms - ethnology ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - ethnology ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; DNA Mismatch Repair - genetics ; DNA-Binding Proteins - genetics ; Epithelial Cell Adhesion Molecule - genetics ; Europe - ethnology ; Female ; Humans ; Male ; Middle Aged ; Mismatch Repair Endonuclease PMS2 - genetics ; MutL Protein Homolog 1 - genetics ; MutS Homolog 2 Protein - genetics ; Polymorphism, Single Nucleotide ; Risk Assessment ; Risk Factors</subject><ispartof>JNCI cancer spectrum, 2021-04, Vol.5 (2)</ispartof><rights>The Author(s) 2021. Published by Oxford University Press. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-fa9afcbe25c1a56f7fadcc7060f12fd3ba65d2015eaebe8816ffbe1787a52ea33</citedby><cites>FETCH-LOGICAL-c424t-fa9afcbe25c1a56f7fadcc7060f12fd3ba65d2015eaebe8816ffbe1787a52ea33</cites><orcidid>0000-0003-3017-0871 ; 0000-0001-8535-6003 ; 0000-0002-8964-6160</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/PMC8062848/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062848/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33928216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jenkins, Mark A</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Lai, John</creatorcontrib><creatorcontrib>Makalic, Enes</creatorcontrib><creatorcontrib>Dite, Gillian S</creatorcontrib><creatorcontrib>Win, Aung K</creatorcontrib><creatorcontrib>Clendenning, Mark</creatorcontrib><creatorcontrib>Winship, Ingrid M</creatorcontrib><creatorcontrib>Hayes, Richard B</creatorcontrib><creatorcontrib>Huyghe, Jeroen R</creatorcontrib><creatorcontrib>Peters, Ulrike</creatorcontrib><creatorcontrib>Gallinger, Steven</creatorcontrib><creatorcontrib>Marchand, Loïc Le</creatorcontrib><creatorcontrib>Figueiredo, Jane C</creatorcontrib><creatorcontrib>Pai, Rish K</creatorcontrib><creatorcontrib>Newcomb, Polly A</creatorcontrib><creatorcontrib>Church, James M</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><title>Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer</title><title>JNCI cancer spectrum</title><addtitle>JNCI Cancer Spectr</addtitle><description>Abstract
It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.</description><subject>Brief Communications</subject><subject>Colorectal Neoplasms - ethnology</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - ethnology</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>DNA Mismatch Repair - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epithelial Cell Adhesion Molecule - genetics</subject><subject>Europe - ethnology</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mismatch Repair Endonuclease PMS2 - genetics</subject><subject>MutL Protein Homolog 1 - genetics</subject><subject>MutS Homolog 2 Protein - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><issn>2515-5091</issn><issn>2515-5091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1LAzEQxYMoVtSrR8lRD7VJttkmF0GKX1BQ_DiH2eykru4mNdkK_e9d2VoUD55mYH7vzQyPkCPOzjjT2ejV28qm0eINCibEFtkTksuhZJpv_-gH5DClV8YY11pLne-SQZZpoQTP94i_SAlTatC3NDgK9D7Uqzn6ytKHKr3RRxsiUhcinYa6a20LNZ2CtxhpG-h9xLKybc92-tnK2xf6uPJlDA3-1RyQHQd1wsN13SfPV5dP05vh7O76dnoxG9qxGLdDBxqcLVBIy0HmbuKgtHbCcua4cGVWQC5LwbhEwAKV4rlzBfKJmoAUCFm2T85738WyaLC03XsRarOIVQNxZQJU5vfEVy9mHj6MYrlQY9UZnKwNYnhfYmpNUyWLdQ0ewzIZIQVTUqpMd-hZj9oYUoroNms4M185mT4ns86pExz_PG6Df6fSAac9EJaL_8w-AYhfoiE</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Jenkins, Mark A</creator><creator>Buchanan, Daniel D</creator><creator>Lai, John</creator><creator>Makalic, Enes</creator><creator>Dite, Gillian S</creator><creator>Win, Aung K</creator><creator>Clendenning, Mark</creator><creator>Winship, Ingrid M</creator><creator>Hayes, Richard B</creator><creator>Huyghe, Jeroen R</creator><creator>Peters, Ulrike</creator><creator>Gallinger, Steven</creator><creator>Marchand, Loïc Le</creator><creator>Figueiredo, Jane C</creator><creator>Pai, Rish K</creator><creator>Newcomb, Polly A</creator><creator>Church, James M</creator><creator>Casey, Graham</creator><creator>Hopper, John L</creator><general>Oxford University Press</general><scope>TOX</scope><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3017-0871</orcidid><orcidid>https://orcid.org/0000-0001-8535-6003</orcidid><orcidid>https://orcid.org/0000-0002-8964-6160</orcidid></search><sort><creationdate>20210401</creationdate><title>Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer</title><author>Jenkins, Mark A ; Buchanan, Daniel D ; Lai, John ; Makalic, Enes ; Dite, Gillian S ; Win, Aung K ; Clendenning, Mark ; Winship, Ingrid M ; Hayes, Richard B ; Huyghe, Jeroen R ; Peters, Ulrike ; Gallinger, Steven ; Marchand, Loïc Le ; Figueiredo, Jane C ; Pai, Rish K ; Newcomb, Polly A ; Church, James M ; Casey, Graham ; Hopper, John L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-fa9afcbe25c1a56f7fadcc7060f12fd3ba65d2015eaebe8816ffbe1787a52ea33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Brief Communications</topic><topic>Colorectal Neoplasms - ethnology</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - ethnology</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>DNA Mismatch Repair - genetics</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epithelial Cell Adhesion Molecule - genetics</topic><topic>Europe - ethnology</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mismatch Repair Endonuclease PMS2 - genetics</topic><topic>MutL Protein Homolog 1 - genetics</topic><topic>MutS Homolog 2 Protein - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jenkins, Mark A</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Lai, John</creatorcontrib><creatorcontrib>Makalic, Enes</creatorcontrib><creatorcontrib>Dite, Gillian S</creatorcontrib><creatorcontrib>Win, Aung K</creatorcontrib><creatorcontrib>Clendenning, Mark</creatorcontrib><creatorcontrib>Winship, Ingrid M</creatorcontrib><creatorcontrib>Hayes, Richard B</creatorcontrib><creatorcontrib>Huyghe, Jeroen R</creatorcontrib><creatorcontrib>Peters, Ulrike</creatorcontrib><creatorcontrib>Gallinger, Steven</creatorcontrib><creatorcontrib>Marchand, Loïc Le</creatorcontrib><creatorcontrib>Figueiredo, Jane C</creatorcontrib><creatorcontrib>Pai, Rish K</creatorcontrib><creatorcontrib>Newcomb, Polly A</creatorcontrib><creatorcontrib>Church, James M</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JNCI cancer spectrum</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jenkins, Mark A</au><au>Buchanan, Daniel D</au><au>Lai, John</au><au>Makalic, Enes</au><au>Dite, Gillian S</au><au>Win, Aung K</au><au>Clendenning, Mark</au><au>Winship, Ingrid M</au><au>Hayes, Richard B</au><au>Huyghe, Jeroen R</au><au>Peters, Ulrike</au><au>Gallinger, Steven</au><au>Marchand, Loïc Le</au><au>Figueiredo, Jane C</au><au>Pai, Rish K</au><au>Newcomb, Polly A</au><au>Church, James M</au><au>Casey, Graham</au><au>Hopper, John L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer</atitle><jtitle>JNCI cancer spectrum</jtitle><addtitle>JNCI Cancer Spectr</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>5</volume><issue>2</issue><issn>2515-5091</issn><eissn>2515-5091</eissn><abstract>Abstract
It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33928216</pmid><doi>10.1093/jncics/pkab022</doi><orcidid>https://orcid.org/0000-0003-3017-0871</orcidid><orcidid>https://orcid.org/0000-0001-8535-6003</orcidid><orcidid>https://orcid.org/0000-0002-8964-6160</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Brief Communications Colorectal Neoplasms - ethnology Colorectal Neoplasms - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - ethnology Colorectal Neoplasms, Hereditary Nonpolyposis - genetics DNA Mismatch Repair - genetics DNA-Binding Proteins - genetics Epithelial Cell Adhesion Molecule - genetics Europe - ethnology Female Humans Male Middle Aged Mismatch Repair Endonuclease PMS2 - genetics MutL Protein Homolog 1 - genetics MutS Homolog 2 Protein - genetics Polymorphism, Single Nucleotide Risk Assessment Risk Factors |
| title | Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer |
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