UNASSIGNED: We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from a genome-wide association study (GWAS) to assess the causal associations between nine cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z) and six types of digestive system tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract cancer (BTC), colorectal cancer (CRC), gastric carcinoma (GC), and esophageal cancer (EC). We employed the following methods including inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran\'s Q, MR-PRESSO, MR-Egger intercept test and leave-one-out sensitivity analysis. The STROBE-MR checklist for the reporting of MR studies was used in this study.
UNASSIGNED: The risk of HCC increased with high levels of cathepsin G (IVW: p = 0.029, odds ratio (OR) = 1.369, 95% confidence interval (CI) = 1.033-1.814). Similarly, BTC was associated with elevated cathepsin B levels (IVW: p = 0.025, OR = 1.693, 95% CI = 1.070-2.681). Conversely, a reduction in PCa risk was associated with increased cathepsin H levels (IVW: p = 0.027, OR = 0.896, 95% CI = 0.812-0.988). Lastly, high levels of cathepsin L2 were found to lower the risk of CRC (IVW: p = 0.034, OR = 0.814, 95% CI = 0.674-0.985).
UNASSIGNED: Our findings confirm the causal relationship between cathepsins and digestive system tumors, which can offer valuable insights for the diagnosis and treatment of digestive system tumors.
■我们使用来自全基因组关联研究(GWAS)的汇总数据进行了双样本双向孟德尔随机化(MR)研究,以评估九种组织蛋白酶(组织蛋白酶B,E,F,G,H,L2、O、S,和Z)和六种消化系统肿瘤,包括肝细胞癌(HCC),胰腺癌(PCa),胆道癌(BTC),结直肠癌(CRC),胃癌(GC),和食道癌(EC)。我们采用了以下方法,包括方差逆加权(IVW),MR-Egger,加权中位数(WM),Cochran\'sQ,MR-PRESSO,MR-Egger截距检验和留一灵敏度分析。本研究使用STROBE-MR检查表报告MR研究。
■肝癌的风险随着组织蛋白酶G的高水平而增加(IVW:p=0.029,比值比(OR)=1.369,95%置信区间(CI)=1.033-1.814)。同样,BTC与组织蛋白酶B水平升高相关(IVW:p=0.025,OR=1.693,95%CI=1.070-2.681)。相反,PCa风险降低与组织蛋白酶H水平升高相关(IVW:p=0.027,OR=0.896,95%CI=0.812~0.988).最后,发现高水平的组织蛋白酶L2可降低CRC的风险(IVW:p=0.034,OR=0.814,95%CI=0.674~0.985).
■我们的发现证实了组织蛋白酶与消化系统肿瘤之间的因果关系,可以为消化系统肿瘤的诊断和治疗提供有价值的见解。