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  • Title: Genetic variations in the TERT and CLPTM1L gene region and gastrointestinal stromal tumors risk.
    Author: Zhang R, Zhao J, Xu J, Liu F, Xu Y, Bu X, Dai C, Song C.
    Journal: Oncotarget; 2015 Oct 13; 6(31):31360-7. PubMed ID: 26372813.
    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.
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