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The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma
Summary Background The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear. Aim To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis. Methods We included United Kingdo...
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| Published in: | Alimentary pharmacology & therapeutics 2023-09, Vol.58 (6), p.623-631 |
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| creator | Innes, Hamish Morgan, Marsha Y. Hampe, Jochen Stickel, Felix Buch, Stephan |
| description | Summary
Background
The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear.
Aim
To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis.
Methods
We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all‐cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment.
Results
The final sample included 439 patients; 74% had either non‐alcoholic fatty liver disease or alcohol‐related liver disease. There were 321 deaths during a mean follow‐up of 1.9 years per participant. Kaplan–Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively.
In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all‐cause mortality risk (aHR: 0.74; 95% CI: 0.61–0.90; p = 0.003). Other associated factors were Baveno stage 3–4 (aHR: 1.65; 95% CI: 1.05–2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17–0.37; p |
| doi_str_mv | 10.1111/apt.17638 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2840244204</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2857231914</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3888-ca1980100e39e7a47c6ff355d20710bd10cf1a463dae2b5099947b62389c790c3</originalsourceid><addsrcrecordid>eNp10c1q3DAUBWBRGppp2kVeIAi6aRdOrn4sWdlN0iYpBFrodG1k-ZpRsC1HsicM5OHj6aRZBHI3d_NxOHAIOWZwyuY7s8N4yrQSxTuyYELlGQeh3pMFcGUyXjBxSD6mdAcASgP_QA6FlhqElAvyuFojjUlzxUSu9PlqSYfQbrsQh7VPHfU9vfnznekLJqhP1KYUnLcj1vTBj2uaprjxG9vSCnts_EhtM2KkNW6wDUOH_UhDQ9c42DE4bNuptZE6G53vQ2c_kYPGtgk_P_8j8vfqx-ryJrv9df3zcnmbOVEUReYsMwUwABQGtZXaqaYReV5z0AyqmoFrmJVK1BZ5lYMxRupKcVEYpw04cUS-7nOHGO4nTGPZ-bSrY3sMUyp5IYFLyUHO9Msrehem2M_tZpVrLphhO_Vtr1wMKUVsyiH6zsZtyaDcTVLOk5T_JpntyXPiVHVYv8j_G8zgbA8efIvbt5PK5e_VPvIJZ6uTlw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2857231914</pqid></control><display><type>article</type><title>The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma</title><source>Wiley-Blackwell Journals</source><creator>Innes, Hamish ; Morgan, Marsha Y. ; Hampe, Jochen ; Stickel, Felix ; Buch, Stephan</creator><creatorcontrib>Innes, Hamish ; Morgan, Marsha Y. ; Hampe, Jochen ; Stickel, Felix ; Buch, Stephan</creatorcontrib><description>Summary
Background
The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear.
Aim
To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis.
Methods
We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all‐cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment.
Results
The final sample included 439 patients; 74% had either non‐alcoholic fatty liver disease or alcohol‐related liver disease. There were 321 deaths during a mean follow‐up of 1.9 years per participant. Kaplan–Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively.
In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all‐cause mortality risk (aHR: 0.74; 95% CI: 0.61–0.90; p = 0.003). Other associated factors were Baveno stage 3–4 (aHR: 1.65; 95% CI: 1.05–2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17–0.37; p < 0.001).
Conclusions
The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.17638</identifier><identifier>PMID: 37470344</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; cirrhosis ; Diagnosis ; Fatty liver ; Gene polymorphism ; Genetic diversity ; Genetic factors ; Genetic Predisposition to Disease ; genetic susceptibility ; Hepatocellular carcinoma ; Humans ; Liver cancer ; Liver diseases ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Medical prognosis ; Mortality ; Multivariate analysis ; Non-alcoholic Fatty Liver Disease ; Polymorphism ; Polymorphism, Single Nucleotide ; prognosis ; Survival ; therapeutic target</subject><ispartof>Alimentary pharmacology & therapeutics, 2023-09, Vol.58 (6), p.623-631</ispartof><rights>2023 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.</rights><rights>2023. This article 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3888-ca1980100e39e7a47c6ff355d20710bd10cf1a463dae2b5099947b62389c790c3</citedby><cites>FETCH-LOGICAL-c3888-ca1980100e39e7a47c6ff355d20710bd10cf1a463dae2b5099947b62389c790c3</cites><orcidid>0000-0001-6134-1026 ; 0000-0003-0565-1083 ; 0000-0003-2928-015X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapt.17638$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapt.17638$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37470344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Innes, Hamish</creatorcontrib><creatorcontrib>Morgan, Marsha Y.</creatorcontrib><creatorcontrib>Hampe, Jochen</creatorcontrib><creatorcontrib>Stickel, Felix</creatorcontrib><creatorcontrib>Buch, Stephan</creatorcontrib><title>The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary
Background
The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear.
Aim
To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis.
Methods
We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all‐cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment.
Results
The final sample included 439 patients; 74% had either non‐alcoholic fatty liver disease or alcohol‐related liver disease. There were 321 deaths during a mean follow‐up of 1.9 years per participant. Kaplan–Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively.
In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all‐cause mortality risk (aHR: 0.74; 95% CI: 0.61–0.90; p = 0.003). Other associated factors were Baveno stage 3–4 (aHR: 1.65; 95% CI: 1.05–2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17–0.37; p < 0.001).
Conclusions
The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC.</description><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>cirrhosis</subject><subject>Diagnosis</subject><subject>Fatty liver</subject><subject>Gene polymorphism</subject><subject>Genetic diversity</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>genetic susceptibility</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Medical prognosis</subject><subject>Mortality</subject><subject>Multivariate analysis</subject><subject>Non-alcoholic Fatty Liver Disease</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>prognosis</subject><subject>Survival</subject><subject>therapeutic target</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp10c1q3DAUBWBRGppp2kVeIAi6aRdOrn4sWdlN0iYpBFrodG1k-ZpRsC1HsicM5OHj6aRZBHI3d_NxOHAIOWZwyuY7s8N4yrQSxTuyYELlGQeh3pMFcGUyXjBxSD6mdAcASgP_QA6FlhqElAvyuFojjUlzxUSu9PlqSYfQbrsQh7VPHfU9vfnznekLJqhP1KYUnLcj1vTBj2uaprjxG9vSCnts_EhtM2KkNW6wDUOH_UhDQ9c42DE4bNuptZE6G53vQ2c_kYPGtgk_P_8j8vfqx-ryJrv9df3zcnmbOVEUReYsMwUwABQGtZXaqaYReV5z0AyqmoFrmJVK1BZ5lYMxRupKcVEYpw04cUS-7nOHGO4nTGPZ-bSrY3sMUyp5IYFLyUHO9Msrehem2M_tZpVrLphhO_Vtr1wMKUVsyiH6zsZtyaDcTVLOk5T_JpntyXPiVHVYv8j_G8zgbA8efIvbt5PK5e_VPvIJZ6uTlw</recordid><startdate>202309</startdate><enddate>202309</enddate><creator>Innes, Hamish</creator><creator>Morgan, Marsha Y.</creator><creator>Hampe, Jochen</creator><creator>Stickel, Felix</creator><creator>Buch, Stephan</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6134-1026</orcidid><orcidid>https://orcid.org/0000-0003-0565-1083</orcidid><orcidid>https://orcid.org/0000-0003-2928-015X</orcidid></search><sort><creationdate>202309</creationdate><title>The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma</title><author>Innes, Hamish ; Morgan, Marsha Y. ; Hampe, Jochen ; Stickel, Felix ; Buch, Stephan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3888-ca1980100e39e7a47c6ff355d20710bd10cf1a463dae2b5099947b62389c790c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>cirrhosis</topic><topic>Diagnosis</topic><topic>Fatty liver</topic><topic>Gene polymorphism</topic><topic>Genetic diversity</topic><topic>Genetic factors</topic><topic>Genetic Predisposition to Disease</topic><topic>genetic susceptibility</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Medical prognosis</topic><topic>Mortality</topic><topic>Multivariate analysis</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>prognosis</topic><topic>Survival</topic><topic>therapeutic target</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Innes, Hamish</creatorcontrib><creatorcontrib>Morgan, Marsha Y.</creatorcontrib><creatorcontrib>Hampe, Jochen</creatorcontrib><creatorcontrib>Stickel, Felix</creatorcontrib><creatorcontrib>Buch, Stephan</creatorcontrib><collection>Open Access: Wiley-Blackwell Open Access Journals</collection><collection>Wiley Online Library</collection><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>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Innes, Hamish</au><au>Morgan, Marsha Y.</au><au>Hampe, Jochen</au><au>Stickel, Felix</au><au>Buch, Stephan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2023-09</date><risdate>2023</risdate><volume>58</volume><issue>6</issue><spage>623</spage><epage>631</epage><pages>623-631</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><notes>Hamish Innes and Marsha Y Morgan have contributed equally and share first authorship status.</notes><notes>The Handling Editor for this article was Professor Gideon Hirschfield, and it was accepted for publication after full peer‐review.</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Summary
Background
The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear.
Aim
To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis.
Methods
We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all‐cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment.
Results
The final sample included 439 patients; 74% had either non‐alcoholic fatty liver disease or alcohol‐related liver disease. There were 321 deaths during a mean follow‐up of 1.9 years per participant. Kaplan–Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively.
In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all‐cause mortality risk (aHR: 0.74; 95% CI: 0.61–0.90; p = 0.003). Other associated factors were Baveno stage 3–4 (aHR: 1.65; 95% CI: 1.05–2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17–0.37; p < 0.001).
Conclusions
The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37470344</pmid><doi>10.1111/apt.17638</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-6134-1026</orcidid><orcidid>https://orcid.org/0000-0003-0565-1083</orcidid><orcidid>https://orcid.org/0000-0003-2928-015X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology cirrhosis Diagnosis Fatty liver Gene polymorphism Genetic diversity Genetic factors Genetic Predisposition to Disease genetic susceptibility Hepatocellular carcinoma Humans Liver cancer Liver diseases Liver Neoplasms - genetics Liver Neoplasms - pathology Medical prognosis Mortality Multivariate analysis Non-alcoholic Fatty Liver Disease Polymorphism Polymorphism, Single Nucleotide prognosis Survival therapeutic target |
| title | The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma |
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