Journal Article

DKFZ-2022-02965

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset.

Gentiluomo, M. ; Capurso, G. ; Morelli, L. ; Ermini, S. ; Pasquali, C. ; Latiano, A. ; Tavano, F. ; Greenhalf, W. ; Milanetto, A. C. ; Landi, S. ; Roth, S. ; Malecka-Wojciesko, E. ; Costello, E. ; Jamroziak, K. ; Perri, F. ; Boggi, U. ; Basso, D. ; Farinati, F. ; Kaaks, R.DKFZ* ; Vanella, G. ; Gais Zurcher, A. J. ; Archibugi, L. ; Lawlor, R. T. ; Canzian, F.DKFZ* ; Campa, D.

2022
Karger Basel

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Please use a persistent id in citations: doi:10.1159/000524659

Abstract: 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.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.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).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.

Keyword(s): Humans (MeSH) ; Genome-Wide Association Study (MeSH) ; Case-Control Studies (MeSH) ; Telomere: genetics (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Neoplasms (MeSH) ; Pancreatic Neoplasms: genetics (MeSH) ; Acid Anhydride Hydrolases: genetics (MeSH) ; Pancreatic neuroendocrine neoplasms ; Polygenic risk score ; Risk ; Teloscore ; ACYP2 protein, human ; Acid Anhydride Hydrolases

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C055 Genomische Epidemiologie (C055)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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