Abstract
Telomerase reverse transcriptase (TERT) is a gene within the cancer susceptibility region located at Chr5p15.33, which is associated with multiple cancer types. In this study, we validated the association between TERT polymorphisms and gastric cancer (GC) risk with a case-control study in a Chinese Han population. A total of 302 GC patients and 300 control individuals were recruited. We identified three single nucleotide polymorphisms (SNPs) in TERT that were associated with GC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association. The minor alleles of three SNPs were associated with increased GC risk inallelic model analysis. For two of the SNPs, rs10069690 and rs2853676,, the dominant and additive model frequencies were higher in GC cases compared to controls. Further haplotype analysis revealed a protective effect of haplotype “CG” of the TERT gene, while the haplotype “TA” increased GC risk.Our resultsprovide new evidence for the association between TERT and GC susceptibility in the Chinese Han population.
Highlights
Telomerase, a ribonucleoprotein complex that maintains telomere length at the ends of chromosomes, regulates cellular immortality and tumorigenesis
The differences in frequency distributions of alleles between cases and controls were compared by Chi-squared test and three single nucleotide polymorphisms (SNPs) in the Telomerase reverse transcriptase (TERT) gene were associated with gastric cancer (GC) risk at a 5 % level
Chromosome 5p15.33, which contains at least two plausible candidate genes, TERT and CLTPM1L, is a unique cancer susceptibility locus associated with about 10 distinct cancers [3, 4]. telomerase consists of a protein with reverse transcriptase activity encoded by TERT and an RNA component that serves as a template for the telomere repeat
Summary
Telomerase, a ribonucleoprotein complex that maintains telomere length at the ends of chromosomes, regulates cellular immortality and tumorigenesis. The TERT gene, which encodes the catalytic subunit of telomerase, is expressed in most aggressive cancer cells but is silenced in non-immortalized cells. TERT is likely driving increased telomerase activity for these malignant cells. This increased activity enables them to overcome replicative senescence and escape apoptosis, and leads to cell immortality [1, 2]. Recent genome-wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) in TERT are associated with the risk of multiple cancers. Few studies in Han Chinese populations have examined the association between TERT and the risk for GC. We evaluated 3 SNPs in TERT associated www.impactjournals.com/oncotarget with GC risk and found a significant association between these SNPS and GC in a Han Chinese population
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