The Causal Relationships between Mitochondria and Six Types of Cancer: A Mendelian Randomization Study

Abstract

Abstract Background Mitochondria play a pivotal and multifaceted role in the progression of cancer. However, the causal relationship between mitochondria and cancer remains to be elucidated. To enhance comprehension, this study employs Mendelian randomization (MR) to investigate the potential causal links between mitochondria and six types of cancer. Methods Through MR analysis, employing the Inverse Variance Weighted method (IVW), MR-Egger method, and Weighted Median method (WM) to analyze the causal relationships between mitochondria and six types of cancer. Additionally, utilizing Cochran's Q test, leave-one-out test, and MR-Egger test to assess the reliability and stability of the causal relationship, employing Steiger directional test to determine whether mitochondrial-related exposure is an upstream factor leading to cancer. Results We observed a negative correlation between "39S ribosomal protein L34, mitochondrial", and others, with hepatic cancer, while "[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial", and others exhibited a positive correlation with hepatic cancer. "Phenylalanine–tRNA ligase, mitochondrial", and others demonstrated a negative association with colorectal cancer, whereas "Methylmalonyl-CoA epimerase, mitochondrial", and others exhibited a positive correlation with colorectal cancer. "Succinate dehydrogenase assembly factor 2, mitochondrial" exhibited a negative correlation with lung cancer, while "Superoxide dismutase [Mn], mitochondrial levels" showed a positive correlation with lung cancer. "Lon protease homolog, mitochondrial" demonstrated a positive correlation with esophageal cancer. "Iron-sulfur cluster assembly enzyme ISCU, mitochondrial", and others exhibited a negative correlation with thyroid cancer, while "Diablo homolog, mitochondrial", and others showed a positive correlation with thyroid cancer. "ADP-ribose pyrophosphatase, mitochondrial", and others exhibited a negative correlation with breast cancer, while "39S ribosomal protein L34, mitochondrial", and others showed a positive correlation with breast cancer. Conclusions Our findings contribute to a nuanced understanding of the causal relationships between mitochondria and the six types of cancer. Additionally, it was observed that identical single-nucleotide polymorphisms (SNPs) serve as instrumental variables (IVs), influencing different cancers through mitochondrial-related exposures. This study provides relevant evidence for mitochondria to be further explored as targets for treating cancer and improving prognosis. Simultaneously, it also aids subsequent research on treating various cancers through targeting a single SNP.