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. 2024 May 31:15:1428433.
doi: 10.3389/fendo.2024.1428433. eCollection 2024.

Cathepsins and cancer risk: a Mendelian randomization study

Tingting Deng #  1 , Xixue Lu #  2 , Xuemin Jia  2 , Jinxin Du  1 , Lijuan Wang  1   2 , Baorui Cao  1 , Meina Yang  3   4 , Ying Yin  5 , Fanjie Liu  2
Affiliations

Cathepsins and cancer risk: a Mendelian randomization study

Tingting Deng et al. Front Endocrinol (Lausanne). .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Mendelian randomization; cancers; cathepsins; causality; single nucleotide polymorphisms (SNPs).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design and workflow.
Figure 2
Figure 2
Forest plots showed the causal associations between cathepsins and cancers. IVW, inverse variance weighting; CI, confidence interval; FDR, false discovery rate.
Figure 3
Figure 3
Forest plots showed the causal associations between cancers and cathepsins. IVW, inverse variance weighting; CI, confidence interval; FDR, false discovery rate.
See this image and copyright information in PMC

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