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000141291 1001_ $$00000-0003-3220-9944$$aCampa, Daniele$$b0
000141291 245__ $$aGenetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study.
000141291 260__ $$aBognor Regis$$bWiley-Liss$$c2019
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000141291 520__ $$aTelomere 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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000141291 7001_ $$0P:(DE-He78)20cdd3e2d3e6f8de7b2b90ab138c7a88$$aMatarazzi, Martina$$b1
000141291 7001_ $$aGreenhalf, William$$b2
000141291 7001_ $$aBijlsma, Maarten$$b3
000141291 7001_ $$0P:(DE-He78)97343bbd9545a4b87574e74329dabfd1$$aSaum, Kai-Uwe$$b4
000141291 7001_ $$aPasquali, Claudio$$b5
000141291 7001_ $$avan Laarhoven, Hanneke$$b6
000141291 7001_ $$aSzentesi, Andrea$$b7
000141291 7001_ $$aFederici, Francesca$$b8
000141291 7001_ $$aVodicka, Pavel$$b9
000141291 7001_ $$aFunel, Niccola$$b10
000141291 7001_ $$aPezzilli, Raffaele$$b11
000141291 7001_ $$aBueno-de-Mesquita, H Bas$$b12
000141291 7001_ $$aVodickova, Ludmila$$b13
000141291 7001_ $$aBasso, Daniela$$b14
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000141291 7001_ $$aHackert, Thilo$$b16
000141291 7001_ $$00000-0002-4294-6799$$aSoucek, Pavel$$b17
000141291 7001_ $$0P:(DE-He78)0a8ada1f5d2ea05fc3af10cd808bfa9a$$aCuk, Katarina$$b18
000141291 7001_ $$aKaiser, Jörg$$b19
000141291 7001_ $$aSperti, Cosimo$$b20
000141291 7001_ $$aLovecek, Martin$$b21
000141291 7001_ $$aCapurso, Gabriele$$b22
000141291 7001_ $$aMohelnikova-Duchonova, Beatrice$$b23
000141291 7001_ $$aKhaw, Kay-Tee$$b24
000141291 7001_ $$aKönig, Anna-Katharina$$b25
000141291 7001_ $$aKupcinskas, Juozas$$b26
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000141291 7001_ $$aBambi, Franco$$b28
000141291 7001_ $$aArchibugi, Livia$$b29
000141291 7001_ $$aMambrini, Andrea$$b30
000141291 7001_ $$aCavestro, Giulia Martina$$b31
000141291 7001_ $$aLandi, Stefano$$b32
000141291 7001_ $$aHegyi, Péter$$b33
000141291 7001_ $$aIzbicki, Jakob R$$b34
000141291 7001_ $$aGioffreda, Domenica$$b35
000141291 7001_ $$aZambon, Carlo Federico$$b36
000141291 7001_ $$00000-0002-8831-7349$$aTavano, Francesca$$b37
000141291 7001_ $$aTalar-Wojnarowska, Renata$$b38
000141291 7001_ $$aJamroziak, Krzysztof$$b39
000141291 7001_ $$aKey, Timothy J$$b40
000141291 7001_ $$aFave, Gianfranco Delle$$b41
000141291 7001_ $$aStrobel, Oliver$$b42
000141291 7001_ $$aJonaitis, Laimas$$b43
000141291 7001_ $$aAndriulli, Angelo$$b44
000141291 7001_ $$aLawlor, Rita T$$b45
000141291 7001_ $$aPirozzi, Felice$$b46
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000141291 7001_ $$aValsuani, Chiara$$b48
000141291 7001_ $$aVashist, Yogesh K$$b49
000141291 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b50
000141291 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b51$$eLast author
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