Association of telomerase reverse transcriptase gene rs10069690 variant with cancer risk: an updated meta-analysis

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ObjectiveExisting evidence suggests telomerase activation is a crucial step in tumorigenesis. The telomerase reverse transcriptase (TERT), encoded by the human TERT gene, is critical for telomerase expression. The TERT rs10069690 (C > T) variant was identified to be associated with the risk of cancer, however, there have been inconsistent results. Therefore, we performed a comprehensive meta-analysis aiming to clarify the association between this variant and cancer susceptibility.MethodsWe conducted literature search in PubMed, EMbase, MEDLINE and Cochrane Library up to April 30, 2024. Overall, there are 55 studies involving 334,196 patients with cancer and 741,187 controls included in the present study. All statistical analyses were performed by STATA software (version 11.0).ResultsThe pooled results showed a significant association between rs10069690 and an increased risk of cancer under allele model (OR = 1.10, 95% CI: 1.07–1.13, P < 0.001), especially in European and Asian populations. When stratified by cancer types, this variant was associated with elevated risk of breast cancer (OR = 1.11, 95% CI: 1.07–1.15, P < 0.001), ovarian cancer (OR = 1.14, 95% CI: 1.10–1.19, P < 0.001), lung cancer (OR = 1.20, 95% CI: 1.07–1.35, P = 0.003), thyroid cancer (OR = 1.23, 95% CI: 1.15–1.32, P < 0.001), gastric cancer (OR = 1.31, 95% CI: 1.19–1.45, P < 0.001), and renal cell carcinoma (OR = 1.29, 95% CI: 1.07–1.55, P = 0.007), while decreased risk was found for hepatocellular carcinoma, prostate cancer and pancreatic cancer. Our results also indicated that this variant was significantly associated with solid cancer (OR = 1.11, 95% CI: 1.07–1.14, P < 0.001), but not with hematological tumor.ConclusionThis systematic meta-analysis demonstrated that the TERT rs10069690 variant was a risk factor for cancer. However, the effects of this variant may vary in different types of cancer and differ across ethnic populations.