Genetic determinants of telomere length and risk of pancreatic cancer a PANDoRA study /
Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization appro...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2019
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| Sorozat: | INTERNATIONAL JOURNAL OF CANCER
144 No. 6 |
| doi: | 10.1002/ijc.31928 |
| mtmt: | 30306949 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/22005 |
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| 024 | 7 | |a 10.1002/ijc.31928 |2 doi | |
| 024 | 7 | |a 30306949 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Campa Daniele | |
| 245 | 1 | 0 | |a Genetic determinants of telomere length and risk of pancreatic cancer |h [elektronikus dokumentum] : |b a PANDoRA study / |c Campa Daniele |
| 260 | |c 2019 | ||
| 300 | |a 1275-1283 | ||
| 490 | 0 | |a INTERNATIONAL JOURNAL OF CANCER |v 144 No. 6 | |
| 520 | 3 | |a Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54x10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87x10-6 , ptrend = 3.27x10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98x10-9 for highest vs. lowest quintile; p = 1.82x10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. This article is protected by copyright. All rights reserved. | |
| 700 | 0 | 1 | |a Matarazzi Martina |e aut |
| 700 | 0 | 1 | |a Greenhalf William |e aut |
| 700 | 0 | 1 | |a Bijlsma Maarten |e aut |
| 700 | 0 | 1 | |a Saum Kai-Uwe |e aut |
| 700 | 0 | 1 | |a Pasquali Claudio |e aut |
| 700 | 0 | 2 | |a van Laarhoven Hanneke |e aut |
| 700 | 0 | 2 | |a Szentesi Andrea Ildikó |e aut |
| 700 | 0 | 2 | |a Federici Francesca |e aut |
| 700 | 0 | 2 | |a Vodicka Pavel |e aut |
| 700 | 0 | 2 | |a Funel Niccola |e aut |
| 700 | 0 | 2 | |a Pezzilli Raffaele |e aut |
| 700 | 0 | 2 | |a Bueno-de-Mesquita H. Bas |e aut |
| 700 | 0 | 2 | |a Vodickov Ludmila |e aut |
| 700 | 0 | 2 | |a Hegyi Péter |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/22005/1/CampaIntJCancer2019.pdf |z Dokumentum-elérés |