TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

Daniele Campa, Cosmeri Rizzato, Rachael Stolzenberg-Solomon, Paola Pacetti, Pavel Vodicka, Sean P. Cleary, Gabriele Capurso, H. B. Bueno-De-Mesquita, Jens Werner, Maria Gazouli, Katja Butterbach, Audrius Ivanauskas, Nathalia Giese, Gloria M. Petersen, Paola Fogar, Zhaoming Wang, Claudio Bassi, Miroslav Ryska, George E. Theodoropoulos, Charles KooperbergDonghui Li, William Greenhalf, Claudio Pasquali, Thilo Hackert, Charles S. Fuchs, Beatrice Mohelnikova-Duchonova, Cosimo Sperti, Niccola Funel, Aida Karina Dieffenbach, Nicholas J. Wareham, Julie Buring, Ivana Holcátová, Eithne Costello, Carlo Federico Zambon, Juozas Kupcinskas, Harvey A. Risch, Peter Kraft, Paige M. Bracci, Raffaele Pezzilli, Sara H. Olson, Howard D. Sesso, Patricia Hartge, Oliver Strobel, Ewa Małecka-Panas, Kala Visvanathan, Alan A. Arslan, Sergio Pedrazzoli, Pavel Souček, Domenica Gioffreda, Timothy J. Key, Renata Talar-Wojnarowska, Aldo Scarpa, Andrea Mambrini, Eric J. Jacobs, Krzysztof Jamroziak, Alison Klein, Francesca Tavano, Franco Bambi, Stefano Landi, Melissa A. Austin, Ludmila Vodickova, Hermann Brenner, Stephen J. Chanock, Gianfranco Delle Fave, Ada Piepoli, Maurizio Cantore, Wei Zheng, Brian M. Wolpin, Laufey T. Amundadottir, Federico Canzian

Research output: Contribution to journalArticle

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 (r2=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. What's new? Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools.

Original languageEnglish (US)
Pages (from-to)2175-2183
Number of pages9
JournalInternational Journal of Cancer
Volume137
Issue number9
DOIs
StatePublished - Nov 1 2015

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Keywords

  • pancreatic cancer
  • polymorphisms
  • susceptibility
  • telomerase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Campa, D., Rizzato, C., Stolzenberg-Solomon, R., Pacetti, P., Vodicka, P., Cleary, S. P., Capurso, G., Bueno-De-Mesquita, H. B., Werner, J., Gazouli, M., Butterbach, K., Ivanauskas, A., Giese, N., Petersen, G. M., Fogar, P., Wang, Z., Bassi, C., Ryska, M., Theodoropoulos, G. E., ... Canzian, F. (2015). TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. International Journal of Cancer, 137(9), 2175-2183. https://doi.org/10.1002/ijc.29590