Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis
Telomerase reverse transcriptase ( ) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between variants and PCa aggressiveness. Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium fo...
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| Veröffentlicht in: | Cancers 2023-05, Vol.15 (9), p.2650 |
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| creator | Zhan, Yongle Ruan, Xiaohao Liu, Jiacheng Huang, Da Huang, Jingyi Huang, Jinlun Chun, Tsun Tsun Stacia Ng, Ada Tsui-Lin Wu, Yishuo Wei, Gonghong Jiang, Haowen Xu, Danfeng Na, Rong |
| description | Telomerase reverse transcriptase (
) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between
variants and PCa aggressiveness.
Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics).
A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20,
= 4.12 × 10
) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25,
= 3.04 × 10
), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71,
= 2.91 × 10
) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98,
= 3.52 × 10
) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49,
= 0.034). Gene-based analysis showed a significant association of
with PCa (European:
= 3.66 × 10
, Chinese:
= 0.043) and PCa severity (
= 0.006) but not with PCa death (
= 0.171).
polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries. |
| doi_str_mv | 10.3390/cancers15092650 |
| format | Article |
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) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between
variants and PCa aggressiveness.
Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics).
A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20,
= 4.12 × 10
) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25,
= 3.04 × 10
), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71,
= 2.91 × 10
) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98,
= 3.52 × 10
) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49,
= 0.034). Gene-based analysis showed a significant association of
with PCa (European:
= 3.66 × 10
, Chinese:
= 0.043) and PCa severity (
= 0.006) but not with PCa death (
= 0.171).
polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15092650</identifier><identifier>PMID: 37174115</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Algorithms ; Analysis ; Biobanks ; Cancer ; Cell division ; Comorbidity ; Consortia ; Datasets ; Death ; Disease ; Disease susceptibility ; Electronic health records ; Family medical history ; Gene polymorphism ; Genealogy ; Genetic aspects ; Genetic polymorphisms ; Genome-wide association studies ; Genomes ; Genomics ; Health aspects ; Medical prognosis ; Minority & ethnic groups ; Mortality ; Oncology, Experimental ; Phenotypes ; Prostate cancer ; Regions ; Regression analysis ; RNA-directed DNA polymerase ; Single-nucleotide polymorphism ; Software ; Telomerase ; Telomerase reverse transcriptase ; Tumorigenesis ; Tumors</subject><ispartof>Cancers, 2023-05, Vol.15 (9), p.2650</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-f9d51b876b0eef8778b3d4bfaa2977934355b4fde6fcfdef72a92d81479846983</citedby><cites>FETCH-LOGICAL-c489t-f9d51b876b0eef8778b3d4bfaa2977934355b4fde6fcfdef72a92d81479846983</cites><orcidid>0000-0001-7470-5108 ; 0000-0002-7378-1915 ; 0000-0002-6203-9459</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/PMC10177366/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177366/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37174115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhan, Yongle</creatorcontrib><creatorcontrib>Ruan, Xiaohao</creatorcontrib><creatorcontrib>Liu, Jiacheng</creatorcontrib><creatorcontrib>Huang, Da</creatorcontrib><creatorcontrib>Huang, Jingyi</creatorcontrib><creatorcontrib>Huang, Jinlun</creatorcontrib><creatorcontrib>Chun, Tsun Tsun Stacia</creatorcontrib><creatorcontrib>Ng, Ada Tsui-Lin</creatorcontrib><creatorcontrib>Wu, Yishuo</creatorcontrib><creatorcontrib>Wei, Gonghong</creatorcontrib><creatorcontrib>Jiang, Haowen</creatorcontrib><creatorcontrib>Xu, Danfeng</creatorcontrib><creatorcontrib>Na, Rong</creatorcontrib><title>Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Telomerase reverse transcriptase (
) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between
variants and PCa aggressiveness.
Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics).
A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20,
= 4.12 × 10
) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25,
= 3.04 × 10
), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71,
= 2.91 × 10
) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98,
= 3.52 × 10
) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49,
= 0.034). Gene-based analysis showed a significant association of
with PCa (European:
= 3.66 × 10
, Chinese:
= 0.043) and PCa severity (
= 0.006) but not with PCa death (
= 0.171).
polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.</description><subject>Algorithms</subject><subject>Analysis</subject><subject>Biobanks</subject><subject>Cancer</subject><subject>Cell division</subject><subject>Comorbidity</subject><subject>Consortia</subject><subject>Datasets</subject><subject>Death</subject><subject>Disease</subject><subject>Disease susceptibility</subject><subject>Electronic health records</subject><subject>Family medical history</subject><subject>Gene polymorphism</subject><subject>Genealogy</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Medical prognosis</subject><subject>Minority & ethnic groups</subject><subject>Mortality</subject><subject>Oncology, Experimental</subject><subject>Phenotypes</subject><subject>Prostate cancer</subject><subject>Regions</subject><subject>Regression analysis</subject><subject>RNA-directed DNA polymerase</subject><subject>Single-nucleotide polymorphism</subject><subject>Software</subject><subject>Telomerase</subject><subject>Telomerase reverse transcriptase</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1r3DAQhk1paUKac29F0EsPcSJZtmT1UszSpoGUhpKehSyPdhVsaSvJC_tz-k8rN2m-qASSGD3vO8wwRfGW4FNKBT7TymkIkTRYVKzBL4rDCvOqZEzULx-9D4rjGG9wXpQSzvjr4oBywmtCmsPi9zk4SFajKz_uJx-2GxuniLxBaQPoGkY_QVAR0A_Y5Vw5FJSLOthtWqKLGlmXf0eVrHcoeXQVfEwqZXTOhnadkWjjCerW6wAx2t0SiEi5AX3zIanRpv1H1KFV1sWyyzXFFPaoc2rcZ-Gb4pVRY4Tju_uo-Pnl8_Xqa3n5_fxi1V2Wum5FKo0YGtK3nPUYwLSctz0d6t4oVQnOBa1p0_S1GYAZnU_DKyWqoSU1F23NREuPik-3vtu5n2DQ4FJQo9wGO6mwl15Z-fTH2Y1c-50kmHBOGcsOH-4cgv815yrkZKOGcVQO_Bxl1RLasIbVIqPvn6E3fg654r9URVvaEvJArdUI0jrjc2K9mMqO1wILRhucqdP_UHkPMFntHRib408EZ7cCvXQ8gLkvkmC5TJZ8NllZ8e5xb-75f3NE_wCkBc2Y</recordid><startdate>20230508</startdate><enddate>20230508</enddate><creator>Zhan, Yongle</creator><creator>Ruan, Xiaohao</creator><creator>Liu, Jiacheng</creator><creator>Huang, Da</creator><creator>Huang, Jingyi</creator><creator>Huang, Jinlun</creator><creator>Chun, Tsun Tsun Stacia</creator><creator>Ng, Ada Tsui-Lin</creator><creator>Wu, Yishuo</creator><creator>Wei, Gonghong</creator><creator>Jiang, Haowen</creator><creator>Xu, Danfeng</creator><creator>Na, Rong</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7470-5108</orcidid><orcidid>https://orcid.org/0000-0002-7378-1915</orcidid><orcidid>https://orcid.org/0000-0002-6203-9459</orcidid></search><sort><creationdate>20230508</creationdate><title>Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis</title><author>Zhan, Yongle ; Ruan, Xiaohao ; Liu, Jiacheng ; Huang, Da ; Huang, Jingyi ; Huang, Jinlun ; Chun, Tsun Tsun Stacia ; Ng, Ada Tsui-Lin ; Wu, Yishuo ; Wei, Gonghong ; Jiang, Haowen ; Xu, Danfeng ; Na, Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-f9d51b876b0eef8778b3d4bfaa2977934355b4fde6fcfdef72a92d81479846983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Algorithms</topic><topic>Analysis</topic><topic>Biobanks</topic><topic>Cancer</topic><topic>Cell division</topic><topic>Comorbidity</topic><topic>Consortia</topic><topic>Datasets</topic><topic>Death</topic><topic>Disease</topic><topic>Disease susceptibility</topic><topic>Electronic health records</topic><topic>Family medical history</topic><topic>Gene polymorphism</topic><topic>Genealogy</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Genome-wide association studies</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>Medical prognosis</topic><topic>Minority & ethnic groups</topic><topic>Mortality</topic><topic>Oncology, Experimental</topic><topic>Phenotypes</topic><topic>Prostate cancer</topic><topic>Regions</topic><topic>Regression analysis</topic><topic>RNA-directed DNA polymerase</topic><topic>Single-nucleotide polymorphism</topic><topic>Software</topic><topic>Telomerase</topic><topic>Telomerase reverse transcriptase</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhan, Yongle</creatorcontrib><creatorcontrib>Ruan, Xiaohao</creatorcontrib><creatorcontrib>Liu, Jiacheng</creatorcontrib><creatorcontrib>Huang, Da</creatorcontrib><creatorcontrib>Huang, Jingyi</creatorcontrib><creatorcontrib>Huang, Jinlun</creatorcontrib><creatorcontrib>Chun, Tsun Tsun Stacia</creatorcontrib><creatorcontrib>Ng, Ada Tsui-Lin</creatorcontrib><creatorcontrib>Wu, Yishuo</creatorcontrib><creatorcontrib>Wei, Gonghong</creatorcontrib><creatorcontrib>Jiang, Haowen</creatorcontrib><creatorcontrib>Xu, Danfeng</creatorcontrib><creatorcontrib>Na, Rong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhan, Yongle</au><au>Ruan, Xiaohao</au><au>Liu, Jiacheng</au><au>Huang, Da</au><au>Huang, Jingyi</au><au>Huang, Jinlun</au><au>Chun, Tsun Tsun Stacia</au><au>Ng, Ada Tsui-Lin</au><au>Wu, Yishuo</au><au>Wei, Gonghong</au><au>Jiang, Haowen</au><au>Xu, Danfeng</au><au>Na, Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2023-05-08</date><risdate>2023</risdate><volume>15</volume><issue>9</issue><spage>2650</spage><pages>2650-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Telomerase reverse transcriptase (
) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between
variants and PCa aggressiveness.
Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics).
A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20,
= 4.12 × 10
) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25,
= 3.04 × 10
), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71,
= 2.91 × 10
) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98,
= 3.52 × 10
) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49,
= 0.034). Gene-based analysis showed a significant association of
with PCa (European:
= 3.66 × 10
, Chinese:
= 0.043) and PCa severity (
= 0.006) but not with PCa death (
= 0.171).
polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37174115</pmid><doi>10.3390/cancers15092650</doi><orcidid>https://orcid.org/0000-0001-7470-5108</orcidid><orcidid>https://orcid.org/0000-0002-7378-1915</orcidid><orcidid>https://orcid.org/0000-0002-6203-9459</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2023-05, Vol.15 (9), p.2650 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10177366 |
| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Algorithms Analysis Biobanks Cancer Cell division Comorbidity Consortia Datasets Death Disease Disease susceptibility Electronic health records Family medical history Gene polymorphism Genealogy Genetic aspects Genetic polymorphisms Genome-wide association studies Genomes Genomics Health aspects Medical prognosis Minority & ethnic groups Mortality Oncology, Experimental Phenotypes Prostate cancer Regions Regression analysis RNA-directed DNA polymerase Single-nucleotide polymorphism Software Telomerase Telomerase reverse transcriptase Tumorigenesis Tumors |
| title | Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis |
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