TY - JOUR
TI - TERT gene harbors multiple variants associated with pancreatic cancer susceptibility
AU - Campa, D.
AU - Rizzato, C.
AU - Stolzenberg-Solomon, R.
AU - Pacetti, P.
AU - Vodicka, P.
AU - Cleary, S.P.
AU - Capurso, G.
AU - Bueno-De-Mesquita, H.B.
AU - Werner, J.
AU - Gazouli, M.
AU - Butterbach, K.
AU - Ivanauskas, A.
AU - Giese, N.
AU - Petersen, G.M.
AU - Fogar, P.
AU - Wang, Z.
AU - Bassi, C.
AU - Ryska, M.
AU - Theodoropoulos, G.E.
AU - Kooperberg, C.
AU - Li, D.
AU - Greenhalf, W.
AU - Pasquali, C.
AU - Hackert, T.
AU - Fuchs, C.S.
AU - Mohelnikova-Duchonova, B.
AU - Sperti, C.
AU - Funel, N.
AU - Dieffenbach, A.K.
AU - Wareham, N.J.
AU - Buring, J.
AU - Holcátová, I.
AU - Costello, E.
AU - Zambon, C.-F.
AU - Kupcinskas, J.
AU - Risch, H.A.
AU - Kraft, P.
AU - Bracci, P.M.
AU - Pezzilli, R.
AU - Olson, S.H.
AU - Sesso, H.D.
AU - Hartge, P.
AU - Strobel, O.
AU - Małecka-Panas, E.
AU - Visvanathan, K.
AU - Arslan, A.A.
AU - Pedrazzoli, S.
AU - Souček, P.
AU - Gioffreda, D.
AU - Key, T.J.
AU - Talar-Wojnarowska, R.
AU - Scarpa, A.
AU - Mambrini, A.
AU - Jacobs, E.J.
AU - Jamroziak, K.
AU - Klein, A.
AU - Tavano, F.
AU - Bambi, F.
AU - Landi, S.
AU - Austin, M.A.
AU - Vodickova, L.
AU - Brenner, H.
AU - Chanock, S.J.
AU - Delle Fave, G.
AU - Piepoli, A.
AU - Cantore, M.
AU - Zheng, W.
AU - Wolpin, B.M.
AU - Amundadottir, L.T.
AU - Canzian, F.
JO - International Journal  of Cancer
PY - 2015
VL - 137
TODO - 9
SP - 2175-2183
PB - Wiley-Liss, Inc.
SN - 0020-7136
TODO - 10.1002/ijc.29590
TODO - 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
TODO - 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.
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