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Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study
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SYSNO ASEP 0495333 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study Author(s) Campa, D. (IT)
Matarazzi, M. (IT)
Greenhalf, W. (GB)
Bijlsma, M. (NL)
Saum, K.U. (DE)
Pasquali, C. (IT)
van Laarhoven, H. (NL)
Szentesi, A. (HU)
Federici, F. (IT)
Vodička, Pavel (UEM-P) RID
Funel, N. (IT)
Pezzilli, R. (IT)
Bueno-de-Mesquita, H. B. (NL)
Vodičková, Ludmila (UEM-P) RID
Basso, D. (IT)
Obazee, O. (DE)
Hackert, T. (DE)
Souček, P. (CZ)
Cuk, K. (DE)
Kaiser, J. (DE)
Sperti, C. (IT)
Loveček, M. (CZ)
Capurso, G. (IT)
Mohelníková-Duchoňová, B. (CZ)
Khaw, K. T. (GB)
König, A.K. (DE)
Kupcinskas, J. (LT)
Kaaks, R. (DE)
Bambi, F. (IT)
Archibugi, L. (IT)
Mambrini, A. (IT)
Cavestro, G.M. (IT)
Landi, S. (IT)
Hegyi, P. (HU)
Izbicki, J.R. (DE)
Gioffreda, D. (IT)
Zambon, C.F. (IT)
Tavano, F. (IT)
Talar-Wojnarowska, R. (PL)
Jamroziak, K. (PL)
Key, T. J. (GB)
Fave, G.D. (IT)
Strobel, O. (DE)
Jonaitis, L. (LT)
Andriulli, A. (IT)
Lawlor, R.T. (IT)
Pirozzi, F. (IT)
Katzke, V. (DE)
Valsuani, Ch. (IT)
Vashist, Y.K. (DE)
Brenner, H. (DE)
Canzian, F. (DE)Source Title International Journal of Cancer. - : Wiley - ISSN 0020-7136
Roč. 144, č. 6 (2019), s. 1275-1283Number of pages 9 s. Language eng - English Country DE - Germany Keywords pancreatic ductal adenocarcinoma ; genetic polymorphisms ; lymphocyte telomere length Subject RIV EB - Genetics ; Molecular Biology OECD category Human genetics Method of publishing Limited access Institutional support UEM-P - RVO:68378041 UT WOS 000459321900007 EID SCOPUS 85056475056 DOI 10.1002/ijc.31928 Annotation 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 x 10(-10)) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80, 95%CI 0.73-0.88, p = 1.87 x 10(-6), p(trend) = 3.27 x 10(-7)). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 x 10(-9) for highest vs. lowest quintile, p = 1.82 x 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. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2020 Electronic address https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31928
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