Association between TERT rs2853669 polymorphism and cancer risk: A meta-analysis of 9,157 cases and 11,073 controls

Abstract

BackgroundIt has been reported that the functional telomerase reverse transcriptase (TERT) rs2853669 polymorphism might contribute to different types of human cancer. However, the association of this mutation with cancer remains controversial. Here, we conducted a meta-analysis to characterize this relationship.Materials and methods/Main resultsA systematic search of studies on the association of TERT rs2853669 polymorphism with all types of cancer was conducted in PubMed, Embase and Cochrane Library. The summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to pool the effect size in a fixed-effects model or a random-effects model where appropriate. A total of 13 articles and 15 case-control studies, including 9,157 cases and 11,073 controls, were included in this meta-analysis. Overall, the pooled results indicated that the rs2853669 polymorphism was significantly associated with increased cancer risk in a homozygote comparison model (CT vs. TT: OR = 1.085, 95% CI: 1.015–1.159, P = 0.016). In the stratified analyses, a significant increased cancer risk was observed in Asian, but not Caucasian patients. A subgroup analysis by cancer type also revealed a significant increase in the risk of lung cancer, but not breast cancer.ConclusionsThe results of this meta-analysis suggest that the TERT rs2853669 polymorphism is associated with a significantly increased risk of cancer, particularly lung cancer, in Asian populations.

Effect of single‐nucleotide polymorphism in TERT promoter on follicular thyroid tumor development

“…SNP rs2853669 has been frequently detected in some malignant tumors such as hepatocellular carcinomas, pulmonary carcinomas, glioblastomas, acute myeloid leukemia, and prostatic carcinomas . Rs2853669 is related to the risk of lung cancer in Asian countries . Ko et al reported that rs2853669 enhanced E2F1 binding and C228T increased ETS2 binding at the TERT promoter, and the combination enhanced TERT promoter methylation and increased TERT promoter activity.…”

“…According to 1000 genome data, the allelic C frequency of this SNP was 24.5% in the population of Tokyo. Liu et al conducted a meta‐analysis to clarify the association between the TERT rs2853669 polymorphism and cancer risk, and the frequencies of CC, CT and TT were 10.4% (207), 43.1% (859), and 46.5% (926) of 1992 Asians in the control group, respectively. The allelic C frequency in the Asian population was found to be 32.0% (1273 of 3984 genes) .…”

“…Liu et al conducted a meta‐analysis to clarify the association between the TERT rs2853669 polymorphism and cancer risk, and the frequencies of CC, CT and TT were 10.4% (207), 43.1% (859), and 46.5% (926) of 1992 Asians in the control group, respectively. The allelic C frequency in the Asian population was found to be 32.0% (1273 of 3984 genes) . The frequencies of rs2853669 in patients with FTC and FTA, as revealed in the current study, were higher than those in a Japanese population and Asian population, although not all follicular neoplasm‐suspected patients undergo surgical resection, which may affect the results of SNP frequency detection in these patients.…”

“…Two common mutations, C228T and C250T, are found at 124 and 146 base pairs upstream of the translation start site, respectively, including in FTC and FTA . The single‐nucleotide polymorphism (SNP) rs2853669 (−245T>C) has been reported in the TERT promoter and is associated with pulmonary carcinoma and glioblastoma risk, shorter overall survival of acute myeloid leukemia, high mortality and recurrence rates of hepatocellular carcinoma, and low breast carcinoma risk . However, no studies have evaluated the role of SNPs in patients with FTC and FTA.…”

Telomere-Related Gene Mutations and Lung Diseases: Pulmonary Fibrosis, Emphysema and Lung Cancer

“…The relationship between TPM and TERT gene expression has shown significantly higher levels of mRNA expression in mesothelioma indicating that genetic alterations of the TERT promoter are a mechanism of TERT mRNA upregulation in mesothelioma 94 . Recent results of a meta-analysis suggested that the TERT rs2853669 polymorphism is associated with a significantly increased risk of cancer, particularly lung cancer; in Asian populations 95 , the TERT rs2853669 T>C polymorphism (SNP), located upstream of the TERT promoter region, has been shown to affect telomerase activity and TL.…”