| Literature DB >> 25940397 |
Daniele Campa1, Cosmeri Rizzato2, Rachael Stolzenberg-Solomon3, Paola Pacetti4, Pavel Vodicka5, Sean P Cleary6, Gabriele Capurso7, H B As Bueno-de-Mesquita8,9,10,11, Jens Werner12, Maria Gazouli13, Katja Butterbach14, Audrius Ivanauskas15, Nathalia Giese12, Gloria M Petersen16, Paola Fogar17, Zhaoming Wang3, Claudio Bassi18, Miroslav Ryska19, George E Theodoropoulos20, Charles Kooperberg21, Donghui Li22, William Greenhalf23, Claudio Pasquali24, Thilo Hackert12, Charles S Fuchs25, Beatrice Mohelnikova-Duchonova26, Cosimo Sperti24, Niccola Funel27, Aida Karina Dieffenbach14,28, Nicholas J Wareham29, Julie Buring30, Ivana Holcátová31, Eithne Costello23, Carlo-Federico Zambon32, Juozas Kupcinskas15, Harvey A Risch33, Peter Kraft34, Paige M Bracci35, Raffaele Pezzilli36, Sara H Olson37, Howard D Sesso30,34, Patricia Hartge3, Oliver Strobel12, Ewa Małecka-Panas38, Kala Visvanathan39, Alan A Arslan40, Sergio Pedrazzoli41, Pavel Souček42, Domenica Gioffreda43, Timothy J Key44, Renata Talar-Wojnarowska38, Aldo Scarpa45, Andrea Mambrini4, Eric J Jacobs46, Krzysztof Jamroziak47, Alison Klein48, Francesca Tavano43, Franco Bambi49, Stefano Landi50, Melissa A Austin51, Ludmila Vodickova5, Hermann Brenner14,28, Stephen J Chanock3, Gianfranco Delle Fave7, Ada Piepoli43, Maurizio Cantore4, Wei Zheng52, Brian M Wolpin25, Laufey T Amundadottir3, Federico Canzian2.
Abstract
A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.Entities:
Keywords: pancreatic cancer; polymorphisms; susceptibility; telomerase
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Year: 2015 PMID： 25940397 PMCID： PMC4548797 DOI： 10.1002/ijc.29590
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.396