Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.
dc.contributor.author | Campa, Daniele | |
dc.contributor.author | Matarazzi, Martina | |
dc.contributor.author | Greenhalf, William | |
dc.contributor.author | Bijlsma, Maarten | |
dc.contributor.author | Saum, Kai-Uwe | |
dc.contributor.author | Pasquali, Claudio | |
dc.contributor.author | van Laarhoven, Hanneke | |
dc.contributor.author | Szentesi, Andrea | |
dc.contributor.author | Federici, Francesca | |
dc.contributor.author | Vodicka, Pavel | |
dc.contributor.author | Funel, Niccola | |
dc.contributor.author | Pezzilli, Raffaele | |
dc.contributor.author | Bueno-de-Mesquita, H Bas | |
dc.contributor.author | Vodickova, Ludmila | |
dc.contributor.author | Basso, Daniela | |
dc.contributor.author | Obazee, Ofure | |
dc.contributor.author | Hackert, Thilo | |
dc.contributor.author | Soucek, Pavel | |
dc.contributor.author | Cuk, Katarina | |
dc.contributor.author | Kaiser, Jörg | |
dc.contributor.author | Sperti, Cosimo | |
dc.contributor.author | Lovecek, Martin | |
dc.contributor.author | Capurso, Gabriele | |
dc.contributor.author | Mohelnikova-Duchonova, Beatrice | |
dc.contributor.author | Khaw, Kay-Tee | |
dc.contributor.author | König, Anna-Katharina | |
dc.contributor.author | Kupcinskas, Juozas | |
dc.contributor.author | Kaaks, Rudolf | |
dc.contributor.author | Bambi, Franco | |
dc.contributor.author | Archibugi, Livia | |
dc.contributor.author | Mambrini, Andrea | |
dc.contributor.author | Cavestro, Giulia Martina | |
dc.contributor.author | Landi, Stefano | |
dc.contributor.author | Hegyi, Péter | |
dc.contributor.author | Izbicki, Jakob R | |
dc.contributor.author | Gioffreda, Domenica | |
dc.contributor.author | Zambon, Carlo Federico | |
dc.contributor.author | Tavano, Francesca | |
dc.contributor.author | Talar-Wojnarowska, Renata | |
dc.contributor.author | Jamroziak, Krzysztof | |
dc.contributor.author | Key, Timothy J | |
dc.contributor.author | Fave, Gianfranco Delle | |
dc.contributor.author | Strobel, Oliver | |
dc.contributor.author | Jonaitis, Laimas | |
dc.contributor.author | Andriulli, Angelo | |
dc.contributor.author | Lawlor, Rita T | |
dc.contributor.author | Pirozzi, Felice | |
dc.contributor.author | Katzke, Verena | |
dc.contributor.author | Valsuani, Chiara | |
dc.contributor.author | Vashist, Yogesh K | |
dc.contributor.author | Brenner, Hermann | |
dc.contributor.author | Canzian, Federico | |
dc.date.accessioned | 2018-11-20T09:42:57Z | |
dc.date.available | 2018-11-20T09:42:57Z | |
dc.date.issued | 2018-10-16 | |
dc.identifier.citation | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2018 Int. J. Cancer | en |
dc.identifier.issn | 1097-0215 | |
dc.identifier.pmid | 30325019 | |
dc.identifier.doi | 20200413 | |
dc.identifier.uri | http://hdl.handle.net/10029/622295 | |
dc.description.abstract | 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 = 1.54 × 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.iso | en | en |
dc.title | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. | en |
dc.type | Article | en |
dc.identifier.journal | Int J Cancer 2018; advance online publication (ahead of print) | en |
html.description.abstract | 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 = 1.54 × 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. |