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| 001 | 141291 | ||
| 005 | 20240229112523.0 | ||
| 024 | 7 | _ | |a 10.1002/ijc.31928 |2 doi |
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| 041 | _ | _ | |a eng |
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| 100 | 1 | _ | |a Campa, Daniele |0 0000-0003-3220-9944 |b 0 |
| 245 | _ | _ | |a Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study. |
| 260 | _ | _ | |a Bognor Regis |c 2019 |b Wiley-Liss |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1555398649_10187 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |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. |
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| 700 | 1 | _ | |a Greenhalf, William |b 2 |
| 700 | 1 | _ | |a Bijlsma, Maarten |b 3 |
| 700 | 1 | _ | |a Saum, Kai-Uwe |0 P:(DE-He78)97343bbd9545a4b87574e74329dabfd1 |b 4 |
| 700 | 1 | _ | |a Pasquali, Claudio |b 5 |
| 700 | 1 | _ | |a van Laarhoven, Hanneke |b 6 |
| 700 | 1 | _ | |a Szentesi, Andrea |b 7 |
| 700 | 1 | _ | |a Federici, Francesca |b 8 |
| 700 | 1 | _ | |a Vodicka, Pavel |b 9 |
| 700 | 1 | _ | |a Funel, Niccola |b 10 |
| 700 | 1 | _ | |a Pezzilli, Raffaele |b 11 |
| 700 | 1 | _ | |a Bueno-de-Mesquita, H Bas |b 12 |
| 700 | 1 | _ | |a Vodickova, Ludmila |b 13 |
| 700 | 1 | _ | |a Basso, Daniela |b 14 |
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| 700 | 1 | _ | |a Hackert, Thilo |b 16 |
| 700 | 1 | _ | |a Soucek, Pavel |0 0000-0002-4294-6799 |b 17 |
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| 700 | 1 | _ | |a Sperti, Cosimo |b 20 |
| 700 | 1 | _ | |a Lovecek, Martin |b 21 |
| 700 | 1 | _ | |a Capurso, Gabriele |b 22 |
| 700 | 1 | _ | |a Mohelnikova-Duchonova, Beatrice |b 23 |
| 700 | 1 | _ | |a Khaw, Kay-Tee |b 24 |
| 700 | 1 | _ | |a König, Anna-Katharina |b 25 |
| 700 | 1 | _ | |a Kupcinskas, Juozas |b 26 |
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| 700 | 1 | _ | |a Bambi, Franco |b 28 |
| 700 | 1 | _ | |a Archibugi, Livia |b 29 |
| 700 | 1 | _ | |a Mambrini, Andrea |b 30 |
| 700 | 1 | _ | |a Cavestro, Giulia Martina |b 31 |
| 700 | 1 | _ | |a Landi, Stefano |b 32 |
| 700 | 1 | _ | |a Hegyi, Péter |b 33 |
| 700 | 1 | _ | |a Izbicki, Jakob R |b 34 |
| 700 | 1 | _ | |a Gioffreda, Domenica |b 35 |
| 700 | 1 | _ | |a Zambon, Carlo Federico |b 36 |
| 700 | 1 | _ | |a Tavano, Francesca |0 0000-0002-8831-7349 |b 37 |
| 700 | 1 | _ | |a Talar-Wojnarowska, Renata |b 38 |
| 700 | 1 | _ | |a Jamroziak, Krzysztof |b 39 |
| 700 | 1 | _ | |a Key, Timothy J |b 40 |
| 700 | 1 | _ | |a Fave, Gianfranco Delle |b 41 |
| 700 | 1 | _ | |a Strobel, Oliver |b 42 |
| 700 | 1 | _ | |a Jonaitis, Laimas |b 43 |
| 700 | 1 | _ | |a Andriulli, Angelo |b 44 |
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| 773 | _ | _ | |a 10.1002/ijc.31928 |0 PERI:(DE-600)1474822-8 |n 6 |p 1275-1283 |t International journal of cancer |v 144 |y 2019 |x 0020-7136 |
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