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Abstract：
UNASSIGNED: Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis.
UNASSIGNED: We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis.
UNASSIGNED: After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027-1.114, P = 0.001, PFDR = 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919-0.975, P = 0.0002, P FDR = 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001-1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001-1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012-1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949-0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902-0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938-0.990, P = 0.006).
UNASSIGNED: Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer.
UNASSIGNED: We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis.
UNASSIGNED: After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027-1.114, P = 0.001, PFDR = 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919-0.975, P = 0.0002, P FDR = 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001-1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001-1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012-1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949-0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902-0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938-0.990, P = 0.006).
UNASSIGNED: Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer.
摘要：
■先前的观察性流行病学研究报道了组织蛋白酶与癌症之间的关联，然而,因果关系是不确定的。本研究使用孟德尔随机化（MR）分析评估了组织蛋白酶与癌症之间的因果关系。
■我们使用公开的全基因组关联研究（GWAS）数据进行双向MR分析。使用逆方差加权(IVW)作为MR分析的主要MR方法。
■错误发现率(FDR)校正后，发现两种组织蛋白酶与癌症风险显着相关：组织蛋白酶H（CTSH）水平增加了肺癌的风险（OR=1.070，95％CI=1.027-1.114，P=0.001，PFDR=0.009），CTSH水平降低了基底细胞癌的风险（OR=0.947，95％CI=0.919-0.975，P=0.0002，PFDR=0.002）。此外,20种癌症对9种组织蛋白酶没有统计学意义.一些未经调整的低P值表型值得一提的是，其中组织蛋白酶O(CTSO)与乳腺癌呈正相关(OR=1.012,95%CI=1.001-1.025,P=0.041),组织蛋白酶S(CTSS)与咽喉癌(OR=1.017,95%CI=1.001-1.034,P=0.043),CTSS与子宫内膜癌(OR=1.055,95%CI=1.012-1.101,P=0.012);组织蛋白酶Z与卵巢癌(CTSZ)呈负相关(OR=0.970,95%CI=0.949-0.991,P=0.006),CTSS与前列腺癌(OR=0.947,95%CI=0.902-0.944,P=0.028),组织蛋白酶E(CTSE)与胰腺癌(OR=0.963,95%CI=0.938-0.990,P=0.006)。
■我们的MR分析显示了组织蛋白酶与癌症之间的因果关系，可能有助于为组织蛋白酶介导的癌症的进一步机制和临床研究提供新的见解。
■我们使用公开的全基因组关联研究（GWAS）数据进行双向MR分析。使用逆方差加权(IVW)作为MR分析的主要MR方法。
■错误发现率(FDR)校正后，发现两种组织蛋白酶与癌症风险显着相关：组织蛋白酶H（CTSH）水平增加了肺癌的风险（OR=1.070，95％CI=1.027-1.114，P=0.001，PFDR=0.009），CTSH水平降低了基底细胞癌的风险（OR=0.947，95％CI=0.919-0.975，P=0.0002，PFDR=0.002）。此外,20种癌症对9种组织蛋白酶没有统计学意义.一些未经调整的低P值表型值得一提的是，其中组织蛋白酶O(CTSO)与乳腺癌呈正相关(OR=1.012,95%CI=1.001-1.025,P=0.041),组织蛋白酶S(CTSS)与咽喉癌(OR=1.017,95%CI=1.001-1.034,P=0.043),CTSS与子宫内膜癌(OR=1.055,95%CI=1.012-1.101,P=0.012);组织蛋白酶Z与卵巢癌(CTSZ)呈负相关(OR=0.970,95%CI=0.949-0.991,P=0.006),CTSS与前列腺癌(OR=0.947,95%CI=0.902-0.944,P=0.028),组织蛋白酶E(CTSE)与胰腺癌(OR=0.963,95%CI=0.938-0.990,P=0.006)。
■我们的MR分析显示了组织蛋白酶与癌症之间的因果关系，可能有助于为组织蛋白酶介导的癌症的进一步机制和临床研究提供新的见解。
