Show simple item record

dc.contributor.authorCampa, Daniele
dc.contributor.authorMatarazzi, Martina
dc.contributor.authorGreenhalf, William
dc.contributor.authorBijlsma, Maarten
dc.contributor.authorSaum, Kai-Uwe
dc.contributor.authorPasquali, Claudio
dc.contributor.authorvan Laarhoven, Hanneke
dc.contributor.authorSzentesi, Andrea
dc.contributor.authorFederici, Francesca
dc.contributor.authorVodicka, Pavel
dc.contributor.authorFunel, Niccola
dc.contributor.authorPezzilli, Raffaele
dc.contributor.authorBueno-de-Mesquita, H Bas
dc.contributor.authorVodickova, Ludmila
dc.contributor.authorBasso, Daniela
dc.contributor.authorObazee, Ofure
dc.contributor.authorHackert, Thilo
dc.contributor.authorSoucek, Pavel
dc.contributor.authorCuk, Katarina
dc.contributor.authorKaiser, Jörg
dc.contributor.authorSperti, Cosimo
dc.contributor.authorLovecek, Martin
dc.contributor.authorCapurso, Gabriele
dc.contributor.authorMohelnikova-Duchonova, Beatrice
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorKönig, Anna-Katharina
dc.contributor.authorKupcinskas, Juozas
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorBambi, Franco
dc.contributor.authorArchibugi, Livia
dc.contributor.authorMambrini, Andrea
dc.contributor.authorCavestro, Giulia Martina
dc.contributor.authorLandi, Stefano
dc.contributor.authorHegyi, Péter
dc.contributor.authorIzbicki, Jakob R
dc.contributor.authorGioffreda, Domenica
dc.contributor.authorZambon, Carlo Federico
dc.contributor.authorTavano, Francesca
dc.contributor.authorTalar-Wojnarowska, Renata
dc.contributor.authorJamroziak, Krzysztof
dc.contributor.authorKey, Timothy J
dc.contributor.authorFave, Gianfranco Delle
dc.contributor.authorStrobel, Oliver
dc.contributor.authorJonaitis, Laimas
dc.contributor.authorAndriulli, Angelo
dc.contributor.authorLawlor, Rita T
dc.contributor.authorPirozzi, Felice
dc.contributor.authorKatzke, Verena
dc.contributor.authorValsuani, Chiara
dc.contributor.authorVashist, Yogesh K
dc.contributor.authorBrenner, Hermann
dc.contributor.authorCanzian, Federico
dc.date.accessioned2018-11-20T09:42:57Z
dc.date.available2018-11-20T09:42:57Z
dc.date.issued2018-10-16
dc.identifier.citationGenetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2018 Int. J. Canceren
dc.identifier.issn1097-0215
dc.identifier.pmid30325019
dc.identifier.doi20200413
dc.identifier.urihttp://hdl.handle.net/10029/622295
dc.description.abstractTelomere 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 = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 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.
dc.language.isoenen
dc.titleGenetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.en
dc.typeArticleen
dc.identifier.journalInt J Cancer 2018; advance online publication (ahead of print)en
html.description.abstractTelomere 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 = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 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 item appears in the following Collection(s)

Show simple item record