Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset
Introduction: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic...
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| Veröffentlicht in: | Neuroendocrinology 2022-11, Vol.112 (12), p.1168-1176 |
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| creator | Gentiluomo, Manuel Capurso, Gabriele Morelli, Luca Ermini, Stefano Pasquali, Claudio Latiano, Anna Tavano, Francesca Greenhalf, William Milanetto, Anna Caterina Landi, Stefano Roth, Susanne Malecka-Wojciesko, Ewa Costello, Eithne Jamroziak, Krzysztof Perri, Francesco Boggi, Ugo Basso, Daniela Farinati, Fabio Kaaks, Rudolf Vanella, Giuseppe Gais Zurcher, Anna-Lea J. Archibugi, Livia Lawlor, Rita T. Canzian, Federico Campa, Daniele |
| description | Introduction: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet. Methods: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN. Results: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33–2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (OR C/C_vs_G/G = 2.27, CI: 1.58–3.27, p = 8.80 × 10 −6 ) and TERT-rs2736100 (OR C/A_vs_C/C = 2.03, CI: 1.42–2.91, p = 1.06 × 10 −4 ). Conclusion: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN. |
| doi_str_mv | 10.1159/000524659 |
| format | Article |
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In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet. Methods: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN. Results: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33–2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (OR C/C_vs_G/G = 2.27, CI: 1.58–3.27, p = 8.80 × 10 −6 ) and TERT-rs2736100 (OR C/A_vs_C/C = 2.03, CI: 1.42–2.91, p = 1.06 × 10 −4 ). Conclusion: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN.</description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000524659</identifier><identifier>PMID: 35472852</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Acid Anhydride Hydrolases - genetics ; Case-Control Studies ; Genome-Wide Association Study ; Humans ; Medical research ; Medicine, Experimental ; Neoplasms ; Pancreatic Neoplasms - genetics ; Polymorphism, Single Nucleotide - genetics ; Research Article ; Telomere - genetics ; Telomeres ; Tumors</subject><ispartof>Neuroendocrinology, 2022-11, Vol.112 (12), p.1168-1176</ispartof><rights>2022 S. Karger AG, Basel</rights><rights>2022 S. Karger AG, Basel.</rights><rights>COPYRIGHT 2022 S. Karger AG</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-2591d69bcc90f53aa47168af149d95847b2cfc86179c7ec47f2c2be4aef05b333</citedby><cites>FETCH-LOGICAL-c435t-2591d69bcc90f53aa47168af149d95847b2cfc86179c7ec47f2c2be4aef05b333</cites><orcidid>0000-0001-8314-8016 ; 0000-0002-0104-8992 ; 0000-0002-0366-9653 ; 0000-0002-7742-9556 ; 0000-0002-5136-4686 ; 0000-0001-8364-6357 ; 0000-0002-0365-5286 ; 0000-0002-1825-1807</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2423,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35472852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gentiluomo, Manuel</creatorcontrib><creatorcontrib>Capurso, Gabriele</creatorcontrib><creatorcontrib>Morelli, Luca</creatorcontrib><creatorcontrib>Ermini, Stefano</creatorcontrib><creatorcontrib>Pasquali, Claudio</creatorcontrib><creatorcontrib>Latiano, Anna</creatorcontrib><creatorcontrib>Tavano, Francesca</creatorcontrib><creatorcontrib>Greenhalf, William</creatorcontrib><creatorcontrib>Milanetto, Anna Caterina</creatorcontrib><creatorcontrib>Landi, Stefano</creatorcontrib><creatorcontrib>Roth, Susanne</creatorcontrib><creatorcontrib>Malecka-Wojciesko, Ewa</creatorcontrib><creatorcontrib>Costello, Eithne</creatorcontrib><creatorcontrib>Jamroziak, Krzysztof</creatorcontrib><creatorcontrib>Perri, Francesco</creatorcontrib><creatorcontrib>Boggi, Ugo</creatorcontrib><creatorcontrib>Basso, Daniela</creatorcontrib><creatorcontrib>Farinati, Fabio</creatorcontrib><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Vanella, Giuseppe</creatorcontrib><creatorcontrib>Gais Zurcher, Anna-Lea J.</creatorcontrib><creatorcontrib>Archibugi, Livia</creatorcontrib><creatorcontrib>Lawlor, Rita T.</creatorcontrib><creatorcontrib>Canzian, Federico</creatorcontrib><creatorcontrib>Campa, Daniele</creatorcontrib><title>Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset</title><title>Neuroendocrinology</title><addtitle>Neuroendocrinology</addtitle><description>Introduction: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet. Methods: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN. Results: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33–2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (OR C/C_vs_G/G = 2.27, CI: 1.58–3.27, p = 8.80 × 10 −6 ) and TERT-rs2736100 (OR C/A_vs_C/C = 2.03, CI: 1.42–2.91, p = 1.06 × 10 −4 ). Conclusion: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN.</description><subject>Acid Anhydride Hydrolases - genetics</subject><subject>Case-Control Studies</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Neoplasms</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Research Article</subject><subject>Telomere - genetics</subject><subject>Telomeres</subject><subject>Tumors</subject><issn>0028-3835</issn><issn>1423-0194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0c9rFDEUB_Agil2rB-8iA170MDU_J5PjUmtdWLai9RwymZc1OjNZkwza_96UXVcKSw4hL5_vC-Eh9JLgC0KEeo8xFpQ3Qj1CC8IpqzFR_DFaYEzbmrVMnKFnKf0ojCpGn6IzJrikraALZK9hguytGYa76gNkiKOfoK9uYQgjRKjWMG3z92qVqmVKwXqTy-1vX0qfzWQjmBKuNjDHAFMfbCzpcgy7waQxVTdTgvwcPXFmSPDisJ-jbx-vbi8_1eub69Xlcl1bzkSuqVCkb1RnrcJOMGO4JE1rHOGqV6LlsqPW2bYhUlkJlktHLe2AG3BYdIyxc_R233cXw68ZUtajTxaGwUwQ5qRpIxqKsZKi0Dd7ujUDaD-5kKOx91wvJW1aiXGriro4ocrqYfQ2TOB8qT8IvHsQKCbDn7w1c0p69fXLSWtjSCmC07voRxPvNMH6fqz6ONZiXx9-Nncj9Ef5b47___PTxC3EI9hcbfYt9K53Rb06qQ6v_AUBDrAF</recordid><startdate>20221101</startdate><enddate>20221101</enddate><creator>Gentiluomo, Manuel</creator><creator>Capurso, Gabriele</creator><creator>Morelli, Luca</creator><creator>Ermini, Stefano</creator><creator>Pasquali, Claudio</creator><creator>Latiano, Anna</creator><creator>Tavano, Francesca</creator><creator>Greenhalf, William</creator><creator>Milanetto, Anna Caterina</creator><creator>Landi, Stefano</creator><creator>Roth, Susanne</creator><creator>Malecka-Wojciesko, Ewa</creator><creator>Costello, Eithne</creator><creator>Jamroziak, Krzysztof</creator><creator>Perri, Francesco</creator><creator>Boggi, Ugo</creator><creator>Basso, Daniela</creator><creator>Farinati, Fabio</creator><creator>Kaaks, Rudolf</creator><creator>Vanella, Giuseppe</creator><creator>Gais Zurcher, Anna-Lea J.</creator><creator>Archibugi, Livia</creator><creator>Lawlor, Rita T.</creator><creator>Canzian, Federico</creator><creator>Campa, Daniele</creator><general>S. Karger AG</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>ISR</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8314-8016</orcidid><orcidid>https://orcid.org/0000-0002-0104-8992</orcidid><orcidid>https://orcid.org/0000-0002-0366-9653</orcidid><orcidid>https://orcid.org/0000-0002-7742-9556</orcidid><orcidid>https://orcid.org/0000-0002-5136-4686</orcidid><orcidid>https://orcid.org/0000-0001-8364-6357</orcidid><orcidid>https://orcid.org/0000-0002-0365-5286</orcidid><orcidid>https://orcid.org/0000-0002-1825-1807</orcidid></search><sort><creationdate>20221101</creationdate><title>Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset</title><author>Gentiluomo, Manuel ; Capurso, Gabriele ; Morelli, Luca ; Ermini, Stefano ; Pasquali, Claudio ; Latiano, Anna ; Tavano, Francesca ; Greenhalf, William ; Milanetto, Anna Caterina ; Landi, Stefano ; Roth, Susanne ; Malecka-Wojciesko, Ewa ; Costello, Eithne ; Jamroziak, Krzysztof ; Perri, Francesco ; Boggi, Ugo ; Basso, Daniela ; Farinati, Fabio ; Kaaks, Rudolf ; Vanella, Giuseppe ; Gais Zurcher, Anna-Lea J. ; Archibugi, Livia ; Lawlor, Rita T. ; Canzian, Federico ; Campa, Daniele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-2591d69bcc90f53aa47168af149d95847b2cfc86179c7ec47f2c2be4aef05b333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acid Anhydride Hydrolases - genetics</topic><topic>Case-Control Studies</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Neoplasms</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Research Article</topic><topic>Telomere - genetics</topic><topic>Telomeres</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gentiluomo, Manuel</creatorcontrib><creatorcontrib>Capurso, Gabriele</creatorcontrib><creatorcontrib>Morelli, Luca</creatorcontrib><creatorcontrib>Ermini, Stefano</creatorcontrib><creatorcontrib>Pasquali, Claudio</creatorcontrib><creatorcontrib>Latiano, Anna</creatorcontrib><creatorcontrib>Tavano, Francesca</creatorcontrib><creatorcontrib>Greenhalf, William</creatorcontrib><creatorcontrib>Milanetto, Anna Caterina</creatorcontrib><creatorcontrib>Landi, Stefano</creatorcontrib><creatorcontrib>Roth, Susanne</creatorcontrib><creatorcontrib>Malecka-Wojciesko, Ewa</creatorcontrib><creatorcontrib>Costello, Eithne</creatorcontrib><creatorcontrib>Jamroziak, Krzysztof</creatorcontrib><creatorcontrib>Perri, Francesco</creatorcontrib><creatorcontrib>Boggi, Ugo</creatorcontrib><creatorcontrib>Basso, Daniela</creatorcontrib><creatorcontrib>Farinati, Fabio</creatorcontrib><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Vanella, Giuseppe</creatorcontrib><creatorcontrib>Gais Zurcher, Anna-Lea J.</creatorcontrib><creatorcontrib>Archibugi, Livia</creatorcontrib><creatorcontrib>Lawlor, Rita T.</creatorcontrib><creatorcontrib>Canzian, Federico</creatorcontrib><creatorcontrib>Campa, Daniele</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gentiluomo, Manuel</au><au>Capurso, Gabriele</au><au>Morelli, Luca</au><au>Ermini, Stefano</au><au>Pasquali, Claudio</au><au>Latiano, Anna</au><au>Tavano, Francesca</au><au>Greenhalf, William</au><au>Milanetto, Anna Caterina</au><au>Landi, Stefano</au><au>Roth, Susanne</au><au>Malecka-Wojciesko, Ewa</au><au>Costello, Eithne</au><au>Jamroziak, Krzysztof</au><au>Perri, Francesco</au><au>Boggi, Ugo</au><au>Basso, Daniela</au><au>Farinati, Fabio</au><au>Kaaks, Rudolf</au><au>Vanella, Giuseppe</au><au>Gais Zurcher, Anna-Lea J.</au><au>Archibugi, Livia</au><au>Lawlor, Rita T.</au><au>Canzian, Federico</au><au>Campa, Daniele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset</atitle><jtitle>Neuroendocrinology</jtitle><addtitle>Neuroendocrinology</addtitle><date>2022-11-01</date><risdate>2022</risdate><volume>112</volume><issue>12</issue><spage>1168</spage><epage>1176</epage><pages>1168-1176</pages><issn>0028-3835</issn><eissn>1423-0194</eissn><abstract>Introduction: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet. Methods: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN. Results: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33–2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (OR C/C_vs_G/G = 2.27, CI: 1.58–3.27, p = 8.80 × 10 −6 ) and TERT-rs2736100 (OR C/A_vs_C/C = 2.03, CI: 1.42–2.91, p = 1.06 × 10 −4 ). Conclusion: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>35472852</pmid><doi>10.1159/000524659</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8314-8016</orcidid><orcidid>https://orcid.org/0000-0002-0104-8992</orcidid><orcidid>https://orcid.org/0000-0002-0366-9653</orcidid><orcidid>https://orcid.org/0000-0002-7742-9556</orcidid><orcidid>https://orcid.org/0000-0002-5136-4686</orcidid><orcidid>https://orcid.org/0000-0001-8364-6357</orcidid><orcidid>https://orcid.org/0000-0002-0365-5286</orcidid><orcidid>https://orcid.org/0000-0002-1825-1807</orcidid></addata></record> |
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| ispartof | Neuroendocrinology, 2022-11, Vol.112 (12), p.1168-1176 |
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| source | Karger Journals; MEDLINE |
| subjects | Acid Anhydride Hydrolases - genetics Case-Control Studies Genome-Wide Association Study Humans Medical research Medicine, Experimental Neoplasms Pancreatic Neoplasms - genetics Polymorphism, Single Nucleotide - genetics Research Article Telomere - genetics Telomeres Tumors |
| title | Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset |
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