In this study, we demonstrate that mitochondrial dysfunction characterized by genetic predisposition has causal effect on cancers, and identified important putative causal mitochondrial-related genes as follows: 1) FDPS for breast cancer; 2) NUDT5 for prostate cancer; 3) VARS2 for lung cancer and 4) NSUN4 for both breast and prostate cancers. Here, NSUN4 is linked to lung cancer.