title: Genetic variations in the TERT and CLPTM1L gene region and gastrointestinal stromal tumors risk.
abstract: Recent studies have suggested polymorphisms in the TERT and CLPTM1L region are associated with carcinogenesis of many distinct cancer types, including gastrointestinal cancers. However, the contribution of polymorphisms in the TERT and CLPTM1L gene region to gastrointestinal stromal tumors (GISTs) risk is still unknown. We tested the six tagSNPs on TERT and CLPTM1L region with GIST risk, using a population-based, two-stage, case-control study in 2,000 subjects. Functional validation was conducted to validate our findings of TERT rs2736098 and explore its influence on relative telomere length (RTL) in GIST cells. It showed that variant rs2736098 was significantly associated with increased risk of GIST (per allele OR = 1.29, 95% CI: 1.14-1.47, P = 7.03 × 10-5). The difference remain significant after Bonferroni correction (P = 7.03 × 10-5 * 6 = 4.2 × 10-4). Real-time PCR showed carriers of genotype CC have the longest RTL, following by carriers of genotype CT, while carriers of genotype TT have the shortest RTL in GIST tissues (P < 0.001). Our data provide evidence to implicate TERT rs2736098 polymorphism as a novel susceptibility factor for GIST risk.
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, P.R. China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, P.R. China.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, P.R. China.
authors.forename: Chaoliu
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Song
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: CLPTM1L; GIST; TERT; gastrointestinal stromal tumors; polymorphism