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TERT gene harbors multiple variants associated with pancreatic cancer susceptibility
Author(s) -
Campa Daniele,
Rizzato Cosmeri,
StolzenbergSolomon Rachael,
Pacetti Paola,
Vodicka Pavel,
Cleary Sean P.,
Capurso Gabriele,
BuenodeMesquita H. Bas,
Werner Jens,
Gazouli Maria,
Butterbach Katja,
Ivanauskas Audrius,
Giese Nathalia,
Petersen Gloria M.,
Fogar Paola,
Wang Zhaoming,
Bassi Claudio,
Ryska Miroslav,
Theodoropoulos George E.,
Kooperberg Charles,
Li Donghui,
Greenhalf William,
Pasquali Claudio,
Hackert Thilo,
Fuchs Charles S.,
MohelnikovaDuchonova Beatrice,
Sperti Cosimo,
Funel Niccola,
Dieffenbach Aida Karina,
Wareham Nicholas J.,
Buring Julie,
Holcátová Ivana,
Costello Eithne,
Zambon CarloFederico,
Kupcinskas Juozas,
Risch Harvey A.,
Kraft Peter,
Bracci Paige M.,
Pezzilli Raffaele,
Olson Sara H.,
Sesso Howard D.,
Hartge Patricia,
Strobel Oliver,
MałeckaPanas Ewa,
Visvanathan Kala,
Arslan Alan A.,
Pedrazzoli Sergio,
Souček Pavel,
Gioffreda Domenica,
Key Timothy J.,
TalarWojnarowska Renata,
Scarpa Aldo,
Mambrini Andrea,
Jacobs Eric J.,
Jamroziak Krzysztof,
Klein Alison,
Tavano Francesca,
Bambi Franco,
Landi Stefano,
Austin Melissa A.,
Vodickova Ludmila,
Brenner Hermann,
Chanock Stephen J.,
Delle Fave Gianfranco,
Piepoli Ada,
Cantore Maurizio,
Zheng Wei,
Wolpin Brian M.,
Amundadottir Laufey T.,
Canzian Federico
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29590
Subject(s) - pancreatic cancer , linkage disequilibrium , single nucleotide polymorphism , odds ratio , biology , locus (genetics) , telomerase rna component , genetics , cancer , medicine , genotype , oncology , gene , telomerase reverse transcriptase , telomerase
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.