TY  - JOUR
AU  - Gentiluomo, Manuel
AU  - Capurso, Gabriele
AU  - Morelli, Luca
AU  - Ermini, Stefano
AU  - Pasquali, Claudio
AU  - Latiano, Anna
AU  - Tavano, Francesca
AU  - Greenhalf, William
AU  - Milanetto, Anna Caterina
AU  - Landi, Stefano
AU  - Roth, Susanne
AU  - Malecka-Wojciesko, Ewa
AU  - Costello, Eithne
AU  - Jamroziak, Krzysztof
AU  - Perri, Francesco
AU  - Boggi, Ugo
AU  - Basso, Daniela
AU  - Farinati, Fabio
AU  - Kaaks, Rudolf
AU  - Vanella, Giuseppe
AU  - Gais Zurcher, Anna-Lea J
AU  - Archibugi, Livia
AU  - Lawlor, Rita T
AU  - Canzian, Federico
AU  - Campa, Daniele
TI  - Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset.
JO  - Neuroendocrinology
VL  - 112
IS  - 12
SN  - 0028-3835
CY  - Basel
PB  - Karger
M1  - DKFZ-2022-02965
SP  - 1168 - 1176
PY  - 2022
AB  - 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.
KW  - Humans
KW  - Genome-Wide Association Study
KW  - Case-Control Studies
KW  - Telomere: genetics
KW  - Polymorphism, Single Nucleotide: genetics
KW  - Neoplasms
KW  - Pancreatic Neoplasms: genetics
KW  - Acid Anhydride Hydrolases: genetics
KW  - Pancreatic neuroendocrine neoplasms (Other)
KW  - Polygenic risk score (Other)
KW  - Risk (Other)
KW  - Teloscore (Other)
KW  - ACYP2 protein, human (NLM Chemicals)
KW  - Acid Anhydride Hydrolases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35472852
DO  - DOI:10.1159/000524659
UR  - https://inrepo02.dkfz.de/record/182838
ER  -