@article{3087875,
    title = "TERT gene harbors multiple variants associated with pancreatic cancer susceptibility",
    author = "Campa, D. and Rizzato, C. and Stolzenberg-Solomon, R. and Pacetti, P. and Vodicka, P. and Cleary, S.P. and Capurso, G. and Bueno-De-Mesquita, H.B. and Werner, J. and Gazouli, M. and Butterbach, K. and Ivanauskas, A. and Giese, N. and Petersen, G.M. and Fogar, P. and Wang, Z. and Bassi, C. and Ryska, M. and Theodoropoulos, G.E. and Kooperberg, C. and Li, D. and Greenhalf, W. and Pasquali, C. and Hackert, T. and Fuchs, C.S. and Mohelnikova-Duchonova, B. and Sperti, C. and Funel, N. and Dieffenbach, A.K. and Wareham, N.J. and Buring, J. and Holcátová, I. and Costello, E. and Zambon, C.-F. and Kupcinskas, J. and Risch, H.A. and Kraft, P. and Bracci, P.M. and Pezzilli, R. and Olson, S.H. and Sesso, H.D. and Hartge, P. and Strobel, O. and Małecka-Panas, E. and Visvanathan, K. and Arslan, A.A. and Pedrazzoli, S. and Souček, P. and Gioffreda, D. and Key, T.J. and Talar-Wojnarowska, R. and Scarpa, A. and Mambrini, A. and Jacobs, E.J. and Jamroziak, K. and Klein, A. and Tavano, F. and Bambi, F. and Landi, S. and Austin, M.A. and Vodickova, L. and Brenner, H. and Chanock, S.J. and Delle Fave, G. and Piepoli, A. and Cantore, M. and Zheng, W. and Wolpin, B.M. and Amundadottir, L.T. and Canzian, F.",
    journal = "International Journal  of Cancer",
    year = "2015",
    volume = "137",
    number = "9",
    pages = "2175-2183",
    publisher = "Wiley-Liss, Inc.",
    issn = "0020-7136",
    doi = "10.1002/ijc.29590",
    keywords = "telomerase reverse transcriptase;  telomerase;  TERT protein, human, adolescent;  adult;  aged;  Article;  cancer risk;  cancer susceptibility;  chromosome 5p;  CLPTM1L gene;  controlled study;  disease association;  female;  gene;  gene linkage disequilibrium;  gene locus;  genetic variability;  human;  major clinical study;  male;  pancreas cancer;  priority journal;  single nucleotide polymorphism;  TERC gene;  TERT gene;  very elderly;  case control study;  genetic predisposition;  genetics;  middle aged;  mutation;  pancreas carcinoma;  pancreas tumor;  young adult, Adolescent;  Adult;  Aged;  Aged, 80 and over;  Carcinoma, Pancreatic Ductal;  Case-Control Studies;  Female;  Genetic Predisposition to Disease;  Humans;  Linkage Disequilibrium;  Male;  Middle Aged;  Mutation;  Pancreatic Neoplasms;  Polymorphism, Single Nucleotide;  Telomerase;  Young Adult",
    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. © 2015 UICC."
}