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However, the associations between mitochondrial DNA copy number (mtDNA\u2010CN) and cancer risk are controversial. Mendelian randomization (MR) analyses were performed using three independent instrumental variables (IVs) to explore potential associations between mtDNA\u2010CN and 20 types of cancer. The three sets of IVs were primarily obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. The outcome data of cancers were investigated using summary statistics from the FinnGen cohort. The potential causal associations were evaluated using the MR\u2010Egger regression, weighted median, inverse\u2010variance weighted (IVW), and weighted mode methods. The robustness of IVW estimates was validated using leave\u2010one\u2010out sensitivity analysis. Additionally, a meta\u2010analysis was conducted to pool results from three sets of IVs. The results revealed that genetically predicted mtDNA\u2010CN was not associated with cancer risk (odds ratio\u2009=\u20091.02; 95% confidence interval: 0.95\u20131.10). Subgroup analyses indicated no causal association between mtDNA\u2010CN and breast, lung, prostate, skin, colorectal, gastric, liver, cervical uteri, esophageal, thyroid, bladder, pancreas, kidney, corpus uteri, ovary, brain, larynx, and anus cancers. It was observed that mtDNA\u2010CN was associated with lip, oral cavity, and testis cancers. However, these results should be interpreted with caution because a small number of patients with lip and oral cavity or testis cancers were included. The comprehensive MR analysis demonstrated that mtDNA\u2010CN is not a suitable biomarker for tumor risk assessment.<\/jats:p>","DOI":"10.1002\/ijc.34833","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T04:44:48Z","timestamp":1703738688000},"page":"1504-1513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Mitochondrial <scp>DNA<\/scp> copy number and cancer risks: A comprehensive Mendelian randomization analysis"],"prefix":"10.1002","volume":"154","author":[{"given":"Xianlei","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital Ningbo University (Ningbo Medical Center Lihuili Hospital)  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Lihuili Affiliated 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