目的:现有证据表明,端粒酶激活是肿瘤发生的关键步骤。端粒酶逆转录酶(TERT),由人类TERT基因编码,端粒酶的表达至关重要。TERTrs10069690(C>T)变体被鉴定为与癌症风险相关,然而,结果不一致。因此,我们进行了一项全面的荟萃分析,旨在阐明该变异与癌症易感性之间的关联.
方法:我们在PubMed,EMBase,截至2024年4月30日,MEDLINE和Cochrane图书馆。总的来说,本研究共纳入55项研究,涉及334,196例癌症患者和741,187例对照.所有统计分析均通过STATA软件(版本11.0)进行。
结果:汇总结果显示,在等位基因模型下,rs10069690与癌症风险增加之间存在显着关联(OR=1.10,95%CI:1.07-1.13,P<0.001),尤其是在欧洲和亚洲人群中。当按癌症类型分层时,该变异与乳腺癌风险升高相关(OR=1.11,95%CI:1.07-1.15,P<0.001),卵巢癌(OR=1.14,95%CI:1.10-1.19,P<0.001),肺癌(OR=1.20,95%CI:1.07-1.35,P=0.003),甲状腺癌(OR=1.23,95%CI:1.15-1.32,P<0.001),胃癌(OR=1.31,95%CI:1.19-1.45,P<0.001),和肾细胞癌(OR=1.29,95%CI:1.07-1.55,P=0.007),虽然发现肝细胞癌的风险降低,前列腺癌和胰腺癌.我们的结果还表明该变异与实体癌显著相关(OR=1.11,95%CI:1.07-1.14,P<0.001),但不是血液肿瘤。
结论:本系统荟萃分析表明TERTrs10069690变异是癌症的危险因素。然而,这种变异的影响可能在不同类型的癌症中有所不同,并且在不同种族人群中也有所不同。
OBJECTIVE: Existing 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.
METHODS: We 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).
RESULTS: The 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.
CONCLUSIONS: This 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.