Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, P.R. China.
The First Clinical Medical School, Guangxi Medical University, Nanning, Guangxi, P.R. China.
Cancer Med. 2023 Apr;12(8):9937-9944. doi: 10.1002/cam4.5702. Epub 2023 Mar 7.
Hepatocellular carcinoma (HCC) is a common cancer threatening the public health globally. Although HCC has been associated with the telomere length (TL), the causal relationship between them is not well understood. Therefore, we attempted to explore the linear causal relationship between TL and HCC through Mendelian randomization (MR) analysis among Asian and European populations.
The summary statistics of TL-associated single nucleotide polymorphisms (SNPs) were obtained from a genome-wide association study (GWAS) in the Asian population (N = 23,096). The data of TL-associated SNPs in the European population (N = 472,174) and the GWAS summary statistics of HCC in the Asian population (1866 cases, 195,745 controls) as well as the European population (168 cases, 372,016 controls) were downloaded from the public GWAS database. Two-sample MR was performed using inverse variance weighting (IVW), weighted median estimate, MR-Egger regression, weighted-mode estimate, and simple-mode estimate methods. Sensitivity analysis was performed to text the primary results' robustness.
Nine SNPs associated with TL in Asian populations and 98 SNPs in European populations were selected as instrumental variables. No linear causal relationship between heritable TL and the HCC risk was recorded in the Asian (IVW analysis odds ratio [OR] = 1.023, 95% confidence interval [CI] 0.745, 1.405, p = 0.887) and European populations (IVW analysis OR = 0.487, 95% CI 0.180, 1.320, p = 0.157). Other methods also achieved similar outcomes. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.
No linear causal association was recorded between heritable TL and HCC in Asian and European populations.
肝细胞癌（HCC）是一种威胁全球公众健康的常见癌症。尽管 HCC 与端粒长度（TL）有关，但它们之间的因果关系尚不清楚。因此，我们试图通过亚洲和欧洲人群中的孟德尔随机化（MR）分析来探索 TL 与 HCC 之间的线性因果关系。
从亚洲人群的全基因组关联研究（GWAS）中获得了与 TL 相关的单核苷酸多态性（SNP）的汇总统计信息（N=23096）。从公共 GWAS 数据库中下载了欧洲人群中与 TL 相关的 SNP 数据（N=472174）以及亚洲人群（1866 例病例，195745 例对照）和欧洲人群（168 例病例，372016 例对照）的 HCC GWAS 汇总统计信息。使用逆方差加权（IVW）、加权中位数估计、MR-Egger 回归、加权模式估计和简单模式估计方法进行两样本 MR。进行敏感性分析以检验主要结果的稳健性。
选择亚洲人群中与 TL 相关的 9 个 SNP 和欧洲人群中的 98 个 SNP 作为工具变量。在亚洲人群中，遗传 TL 与 HCC 风险之间没有线性因果关系（IVW 分析比值比 [OR]=1.023，95%置信区间 [CI]0.745，1.405，p=0.887）和欧洲人群（IVW 分析 OR=0.487，95%CI 0.180，1.320，p=0.157）。其他方法也得出了类似的结果。进行敏感性分析后，未发现异质性和水平偏倚。
在亚洲和欧洲人群中，遗传 TL 与 HCC 之间没有线性因果关系。
