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Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation
The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR...
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| Published in: | European journal of cancer (1990) 2019-10, Vol.120, p.10-19 |
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| container_end_page | 19 |
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| container_title | European journal of cancer (1990) |
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| creator | Yuan, Ping Huang, Sha Bao, Fei-Chao Cao, Jin-Lin Sheng, Hong-Xu Shi, Liang Lv, Wang Hu, Jian |
| description | The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation.
The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients’ clinical outcomes with a median follow-up of 57 months (2–99 months).
The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p |
| doi_str_mv | 10.1016/j.ejca.2019.06.024 |
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The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients’ clinical outcomes with a median follow-up of 57 months (2–99 months).
The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation.
Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.
•T/C allele is significantly associated with telomere parameters in patients without epidermal growth factor receptor (EGFR) mutation.•T/C allele is significantly associated with shorter overall survival in patients without EGFR mutation.•Investigation of telomerase reverse transcriptase-EGFR interacting mechanism in telomere biology need to be focussed in future research.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2019.06.024</identifier><identifier>PMID: 31446212</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Alleles ; Epidermal growth factor ; Epidermal growth factor receptor mutation (EGFR) ; Epidermal growth factor receptors ; Gene expression ; Gene polymorphism ; Growth factors ; Impact analysis ; Lung cancer ; Mutation ; Non-small cell lung cancer (NSCLC) ; Non-small cell lung carcinoma ; Nucleotides ; Parameters ; Polymorphism ; RNA-directed DNA polymerase ; rs2853669 single-nucleotide polymorphism (rs2853669 SNP) ; Single-nucleotide polymorphism ; Small cell lung carcinoma ; Survival ; Survival outcome ; Telomerase ; Telomerase reverse transcriptase ; Telomerase reverse transcriptase (TERT) ; Telomere length ; Therapeutic applications ; Tumors</subject><ispartof>European journal of cancer (1990), 2019-10, Vol.120, p.10-19</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Oct 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-af680d80aedb5dbcc0c32bce025d600831283415885dfe2a152d66b531b735d23</citedby><cites>FETCH-LOGICAL-c384t-af680d80aedb5dbcc0c32bce025d600831283415885dfe2a152d66b531b735d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31446212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Ping</creatorcontrib><creatorcontrib>Huang, Sha</creatorcontrib><creatorcontrib>Bao, Fei-Chao</creatorcontrib><creatorcontrib>Cao, Jin-Lin</creatorcontrib><creatorcontrib>Sheng, Hong-Xu</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Lv, Wang</creatorcontrib><creatorcontrib>Hu, Jian</creatorcontrib><title>Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation.
The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients’ clinical outcomes with a median follow-up of 57 months (2–99 months).
The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation.
Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.
•T/C allele is significantly associated with telomere parameters in patients without epidermal growth factor receptor (EGFR) mutation.•T/C allele is significantly associated with shorter overall survival in patients without EGFR mutation.•Investigation of telomerase reverse transcriptase-EGFR interacting mechanism in telomere biology need to be focussed in future research.</description><subject>Alleles</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptor mutation (EGFR)</subject><subject>Epidermal growth factor receptors</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Growth factors</subject><subject>Impact analysis</subject><subject>Lung cancer</subject><subject>Mutation</subject><subject>Non-small cell lung cancer (NSCLC)</subject><subject>Non-small cell lung carcinoma</subject><subject>Nucleotides</subject><subject>Parameters</subject><subject>Polymorphism</subject><subject>RNA-directed DNA polymerase</subject><subject>rs2853669 single-nucleotide polymorphism (rs2853669 SNP)</subject><subject>Single-nucleotide polymorphism</subject><subject>Small cell lung carcinoma</subject><subject>Survival</subject><subject>Survival outcome</subject><subject>Telomerase</subject><subject>Telomerase reverse transcriptase</subject><subject>Telomerase reverse transcriptase (TERT)</subject><subject>Telomere length</subject><subject>Therapeutic applications</subject><subject>Tumors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAQhiMEokvhBTggS1y4ZBk7cdYrcUEtFKRKXOBsOfak9SqOg-206kvyTEy6bQ8cuHhG9vePZ-avqrccthx49_GwxYM1WwF8v4VuC6J9Vm242u1rUFI8rzawl_taQbs_qV7lfACAnWrhZXXS8LbtBBeb6s-5zzb54CdT_HTFTM7ResrjxOLADLMxBMoLjjFgMhlZwhtMFEsy06qdy3o7pxhiwcTmON6FmOZrnwO79eX6UUuMSSYgQZn5iU1xqnMw48gs0jEu9L01k6Ua97J4jHEpDGfvMBHLrlK8pbfB2ELvCS3OaxKWct_z6-rFYMaMbx7iafXr65efZ9_qyx8X388-X9a2UW2pzdApcAoMul663lqwjegtgpCuA1ANF6ppuVRKugGF4VK4rutlw_tdI51oTqsPx7o09u8Fc9GB9khjmAnjkrUQCqTccdkQ-v4f9BCXNFF3WjSg2p2SfKXEkbIp5pxw0DO5YtKd5qBXt_VBr27r1W0NnSa3SfTuofTSB3RPkkd7Cfh0BJB2ceMx6Ww90oqdp9UV7aL_X_2_9HjB3g</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Yuan, Ping</creator><creator>Huang, Sha</creator><creator>Bao, Fei-Chao</creator><creator>Cao, Jin-Lin</creator><creator>Sheng, Hong-Xu</creator><creator>Shi, Liang</creator><creator>Lv, Wang</creator><creator>Hu, Jian</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>201910</creationdate><title>Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation</title><author>Yuan, Ping ; Huang, Sha ; Bao, Fei-Chao ; Cao, Jin-Lin ; Sheng, Hong-Xu ; Shi, Liang ; Lv, Wang ; Hu, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-af680d80aedb5dbcc0c32bce025d600831283415885dfe2a152d66b531b735d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alleles</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptor mutation (EGFR)</topic><topic>Epidermal growth factor receptors</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Growth factors</topic><topic>Impact analysis</topic><topic>Lung cancer</topic><topic>Mutation</topic><topic>Non-small cell lung cancer (NSCLC)</topic><topic>Non-small cell lung carcinoma</topic><topic>Nucleotides</topic><topic>Parameters</topic><topic>Polymorphism</topic><topic>RNA-directed DNA polymerase</topic><topic>rs2853669 single-nucleotide polymorphism (rs2853669 SNP)</topic><topic>Single-nucleotide polymorphism</topic><topic>Small cell lung carcinoma</topic><topic>Survival</topic><topic>Survival outcome</topic><topic>Telomerase</topic><topic>Telomerase reverse transcriptase</topic><topic>Telomerase reverse transcriptase (TERT)</topic><topic>Telomere length</topic><topic>Therapeutic applications</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Ping</creatorcontrib><creatorcontrib>Huang, Sha</creatorcontrib><creatorcontrib>Bao, Fei-Chao</creatorcontrib><creatorcontrib>Cao, Jin-Lin</creatorcontrib><creatorcontrib>Sheng, Hong-Xu</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Lv, Wang</creatorcontrib><creatorcontrib>Hu, Jian</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Ping</au><au>Huang, Sha</au><au>Bao, Fei-Chao</au><au>Cao, Jin-Lin</au><au>Sheng, Hong-Xu</au><au>Shi, Liang</au><au>Lv, Wang</au><au>Hu, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2019-10</date><risdate>2019</risdate><volume>120</volume><spage>10</spage><epage>19</epage><pages>10-19</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation.
The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients’ clinical outcomes with a median follow-up of 57 months (2–99 months).
The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation.
Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.
•T/C allele is significantly associated with telomere parameters in patients without epidermal growth factor receptor (EGFR) mutation.•T/C allele is significantly associated with shorter overall survival in patients without EGFR mutation.•Investigation of telomerase reverse transcriptase-EGFR interacting mechanism in telomere biology need to be focussed in future research.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31446212</pmid><doi>10.1016/j.ejca.2019.06.024</doi><tpages>10</tpages></addata></record> |
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| ispartof | European journal of cancer (1990), 2019-10, Vol.120, p.10-19 |
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| subjects | Alleles Epidermal growth factor Epidermal growth factor receptor mutation (EGFR) Epidermal growth factor receptors Gene expression Gene polymorphism Growth factors Impact analysis Lung cancer Mutation Non-small cell lung cancer (NSCLC) Non-small cell lung carcinoma Nucleotides Parameters Polymorphism RNA-directed DNA polymerase rs2853669 single-nucleotide polymorphism (rs2853669 SNP) Single-nucleotide polymorphism Small cell lung carcinoma Survival Survival outcome Telomerase Telomerase reverse transcriptase Telomerase reverse transcriptase (TERT) Telomere length Therapeutic applications Tumors |
| title | Discriminating association of a common telomerase reverse transcriptase promoter polymorphism with telomere parameters in non-small cell lung cancer with or without epidermal growth factor receptor mutation |
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