Publications

Authors:

Campa, Daniele; Matarazzi, Martina; Greenhalf, William; Bijlsma, Maarten; Saum, Kai‐uwe; Pasquali, Claudio; van Laarhoven, Hanneke; Szentesi, Andrea; Federici, Francesca; Vodicka, Pavel; Funel, Niccola; Pezzilli, Raffaele; Bueno‐de‐mesquita, H. Bas; Vodickova, Ludmila; Basso, Daniela; Obazee, Ofure; Hackert, Thilo; Soucek, Pavel; Cuk, Katarina; Kaiser, Jörg; Sperti, Cosimo; Lovecek, Martin; Capurso, Gabriele; Mohelnikova‐duchonova, Beatrice; Khaw, Kay‐tee; König, Anna‐katharina; Kupcinskas, Juozas; Kaaks, Rudolf; Bambi, Franco; Archibugi, Livia; Mambrini, Andrea; Cavestro, Giulia Martina; Landi, Stefano; Hegyi, Péter; Izbicki, Jakob R.; Gioffreda, Domenica; Zambon, Carlo Federico; Tavano, Francesca; Talar‐wojnarowska, Renata; Jamroziak, Krzysztof; Key, Timothy J.; Fave, Gianfranco Delle; Strobel, Oliver; Jonaitis, Laimas; Andriulli, Angelo; Lawlor, Rita T.; Pirozzi, Felice; Katzke, Verena; Valsuani, Chiara; Vashist, Yogesh K.; Brenner, Hermann; Canzian, Federico

Title:

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Year:

2019

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

International Journal of Cancer

ISSN of journal:

0020-7136

N° Volume:

144

Number or Folder:

6

Page numbers:

1275-1283

Keyword:

Mendelian randomization; association; genetic polymorphisms; lymphocyte telomere length; pancreatic ductal adenocarcinoma

Short description of contents:

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.

Product ID:

137871

Handle IRIS:

11562/1119567

Last Modified:

December 30, 2024

Bibliographic citation:

Campa, Daniele; Matarazzi, Martina; Greenhalf, William; Bijlsma, Maarten; Saum, Kai‐uwe; Pasquali, Claudio; van Laarhoven, Hanneke; Szentesi, Andrea; Federici, Francesca; Vodicka, Pavel; Funel, Niccola; Pezzilli, Raffaele; Bueno‐de‐mesquita, H. Bas; Vodickova, Ludmila; Basso, Daniela; Obazee, Ofure; Hackert, Thilo; Soucek, Pavel; Cuk, Katarina; Kaiser, Jörg; Sperti, Cosimo; Lovecek, Martin; Capurso, Gabriele; Mohelnikova‐duchonova, Beatrice; Khaw, Kay‐tee; König, Anna‐katharina; Kupcinskas, Juozas; Kaaks, Rudolf; Bambi, Franco; Archibugi, Livia; Mambrini, Andrea; Cavestro, Giulia Martina; Landi, Stefano; Hegyi, Péter; Izbicki, Jakob R.; Gioffreda, Domenica; Zambon, Carlo Federico; Tavano, Francesca; Talar‐wojnarowska, Renata; Jamroziak, Krzysztof; Key, Timothy J.; Fave, Gianfranco Delle; Strobel, Oliver; Jonaitis, Laimas; Andriulli, Angelo; Lawlor, Rita T.; Pirozzi, Felice; Katzke, Verena; Valsuani, Chiara; Vashist, Yogesh K.; Brenner, Hermann; Canzian, Federico, Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study «International Journal of Cancer» , vol. 144 , n. 6 , 2019 , pp. 1275-1283

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