Germline genetics of prostate cancer
Background An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant c...
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| Veröffentlicht in: | The Prostate 2022-08, Vol.82 (S1), p.S3-S12 |
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| container_title | The Prostate |
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| creator | Khan, Hiba M. Cheng, Heather H. |
| description | Background
An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.
Aims
Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.
Results
The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.
Discussion
The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer. |
| doi_str_mv | 10.1002/pros.24340 |
| format | Article |
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An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.
Aims
Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.
Results
The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.
Discussion
The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.</description><identifier>ISSN: 0270-4137</identifier><identifier>ISSN: 1097-0045</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.24340</identifier><identifier>PMID: 35657157</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>BRCA1 ; BRCA1 protein ; BRCA2 ; BRCA2 protein ; Cancer screening ; Castration ; Clinical trials ; Colorectal cancer ; Deoxyribonucleic acid ; DNA ; DNA damage repair ; DNA repair ; Early Detection of Cancer ; Genetic disorders ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic screening ; Germ Cells - pathology ; Germ-Line Mutation ; germline mutations ; Homologous recombination ; Humans ; Lynch syndrome ; Male ; Medical screening ; Metastases ; Metastasis ; MSH2 protein ; MSH6 protein ; Mutation ; p53 Protein ; Pembrolizumab ; Prostate cancer ; Prostate-Specific Antigen - genetics ; Prostatic Neoplasms - pathology ; Reviews ; Risk factors</subject><ispartof>The Prostate, 2022-08, Vol.82 (S1), p.S3-S12</ispartof><rights>2022 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3270-e484adb321609129bd5ac53508a9d58b5a0dd9cfae1d9912f3f16a9869ff95333</citedby><cites>FETCH-LOGICAL-c3270-e484adb321609129bd5ac53508a9d58b5a0dd9cfae1d9912f3f16a9869ff95333</cites><orcidid>0000-0002-1365-0702</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.24340$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.24340$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35657157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Hiba M.</creatorcontrib><creatorcontrib>Cheng, Heather H.</creatorcontrib><title>Germline genetics of prostate cancer</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>Background
An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.
Aims
Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.
Results
The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.
Discussion
The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.</description><subject>BRCA1</subject><subject>BRCA1 protein</subject><subject>BRCA2</subject><subject>BRCA2 protein</subject><subject>Cancer screening</subject><subject>Castration</subject><subject>Clinical trials</subject><subject>Colorectal cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage repair</subject><subject>DNA repair</subject><subject>Early Detection of Cancer</subject><subject>Genetic disorders</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic screening</subject><subject>Germ Cells - pathology</subject><subject>Germ-Line Mutation</subject><subject>germline mutations</subject><subject>Homologous recombination</subject><subject>Humans</subject><subject>Lynch syndrome</subject><subject>Male</subject><subject>Medical screening</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MSH2 protein</subject><subject>MSH6 protein</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Pembrolizumab</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Reviews</subject><subject>Risk factors</subject><issn>0270-4137</issn><issn>1097-0045</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUQIMobk5f_AFS0AcROm-SpmleBBk6hcHEj-eQpuns6MdMWmX_3tbOoT74lId7OPfmIHSMYYwByOXKVm5MAhrADhpiENwHCNguGgLh4AeY8gE6cG4J0OJA9tGAspBxzPgQnU2NLfKsNN7ClKbOtPOq1OuMtaqNp1WpjT1Ee6nKnTnavCP0cnvzPLnzZ_Pp_eR65mvabTJBFKgkpgSHIDARccKUZpRBpETCopgpSBKhU2VwIlogpSkOlYhCkaaCUUpH6Kr3rpq4MIk2ZW1VLlc2K5Rdy0pl8vekzF7lonqXgjAmIGoF5xuBrd4a42pZZE6bPFelqRonScgpZTyEbtfpH3RZNbZsv9dRJIx4xHBLXfSUbos4a9LtMRhkF192qeRX_BY--Xn-Fv2u3QK4Bz6y3Kz_UcmHx_lTL_0ErYiOWA</recordid><startdate>202208</startdate><enddate>202208</enddate><creator>Khan, Hiba M.</creator><creator>Cheng, Heather H.</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1365-0702</orcidid></search><sort><creationdate>202208</creationdate><title>Germline genetics of prostate cancer</title><author>Khan, Hiba M. ; Cheng, Heather H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3270-e484adb321609129bd5ac53508a9d58b5a0dd9cfae1d9912f3f16a9869ff95333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>BRCA1</topic><topic>BRCA1 protein</topic><topic>BRCA2</topic><topic>BRCA2 protein</topic><topic>Cancer screening</topic><topic>Castration</topic><topic>Clinical trials</topic><topic>Colorectal cancer</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage repair</topic><topic>DNA repair</topic><topic>Early Detection of Cancer</topic><topic>Genetic disorders</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic screening</topic><topic>Germ Cells - pathology</topic><topic>Germ-Line Mutation</topic><topic>germline mutations</topic><topic>Homologous recombination</topic><topic>Humans</topic><topic>Lynch syndrome</topic><topic>Male</topic><topic>Medical screening</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MSH2 protein</topic><topic>MSH6 protein</topic><topic>Mutation</topic><topic>p53 Protein</topic><topic>Pembrolizumab</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Reviews</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Hiba M.</creatorcontrib><creatorcontrib>Cheng, Heather H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Hiba M.</au><au>Cheng, Heather H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Germline genetics of prostate cancer</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2022-08</date><risdate>2022</risdate><volume>82</volume><issue>S1</issue><spage>S3</spage><epage>S12</epage><pages>S3-S12</pages><issn>0270-4137</issn><issn>1097-0045</issn><eissn>1097-0045</eissn><abstract>Background
An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.
Aims
Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.
Results
The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.
Discussion
The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35657157</pmid><doi>10.1002/pros.24340</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1365-0702</orcidid></addata></record> |
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| source | Wiley-Blackwell Journals; MEDLINE |
| subjects | BRCA1 BRCA1 protein BRCA2 BRCA2 protein Cancer screening Castration Clinical trials Colorectal cancer Deoxyribonucleic acid DNA DNA damage repair DNA repair Early Detection of Cancer Genetic disorders Genetic diversity Genetic Predisposition to Disease Genetic screening Germ Cells - pathology Germ-Line Mutation germline mutations Homologous recombination Humans Lynch syndrome Male Medical screening Metastases Metastasis MSH2 protein MSH6 protein Mutation p53 Protein Pembrolizumab Prostate cancer Prostate-Specific Antigen - genetics Prostatic Neoplasms - pathology Reviews Risk factors |
| title | Germline genetics of prostate cancer |
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