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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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Main Authors: Gentiluomo, Manuel (Author) , Capurso, Gabriele (Author) , Morelli, Luca (Author) , Ermini, Stefano (Author) , Pasquali, Claudio (Author) , Latiano, Anna (Author) , Tavano, Francesca (Author) , Greenhalf, William (Author) , Milanetto, Anna Caterina (Author) , Landi, Stefano (Author) , Roth, Susanne (Author) , Malecka-Wojciesko, Ewa (Author) , Costello, Eithne (Author) , Jamroziak, Krzysztof (Author) , Perri, Francesco (Author) , Boggi, Ugo (Author) , Basso, Daniela (Author) , Farinati, Fabio (Author) , Kaaks, Rudolf (Author) , Vanella, Giuseppe (Author) , Zurcher, Anna-Lea J. Gais (Author) , Archibugi, Livia (Author) , Lawlor, Rita T. (Author) , Canzian, Federico (Author) , Campa, Daniele (Author)
Format: Article (Journal)
Language:English
Published: November 2022
In: Neuroendocrinology
Year: 2022, Volume: 112, Issue: 12, Pages: 1168-1176
ISSN:1423-0194
DOI:10.1159/000524659
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000524659
Verlag, lizenzpflichtig, Volltext: https://www.karger.com/Article/FullText/524659
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Author Notes:Manuel Gentiluomo, Gabriele Capurso, Luca Morelli, Stefano Ermini, Claudio Pasquali, Anna Latiano, Francesca Tavano, William Greenhalf, Anna Caterina Milanetto, Stefano Landi, Susanne Roth, Ewa Malecka-Wojciesko, Eithne Costello, Krzysztof Jamroziak, Francesco Perri, Ugo Boggi, Daniela Basso, Fabio Farinati, Rudolf Kaaks, Giuseppe Vanella, Anna-Lea J. Gais Zurcher, Livia Archibugi, Rita T. Lawlor, Federico Canzian, Daniele Campa
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Summary: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 (ORC/C_vs_G/G = 2.27, CI: 1.58–3.27, p = 8.80 × 10−6) and TERT-rs2736100 (ORC/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.
Item Description:Gesehen am 01.02.2023
Physical Description:Online Resource
ISSN:1423-0194
DOI:10.1159/000524659

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