ArticlePloS one2019
Association between mitochondrial genetic variation and breast cancer risk: The Multiethnic Cohort.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Unraveling the genetic connections for mitochondrial DNA control region and breast cancer susceptibility.Scientific reports · 2025Article
- Mitochondrial RNA in Inflammation.International journal of biological sciences · 2025Review
- Facts, Dogmas, and Unknowns About Mitochondrial Reactive Oxygen Species in Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Native Hawaiian and Pacific Islander populations in genomic research.NPJ genomic medicine · 2024Review
- Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.Journal of cellular and molecular medicine · 2024Review
- Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer.Genes · 2023Article
- Mitochondrial-nuclear epistasis underlying phenotypic variation in breast cancer pathology.Scientific reports · 2022Article
- Role of mitochondrial translation in remodeling of energy metabolism in ER/PR(+) breast cancer.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundThe mitochondrial genome encodes for thirty-seven proteins, among them thirteen are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process and promoting the production of reactive oxidative species.
methodsTo investigate the association between mitochondrial genetic variation and breast cancer risk, we tested 314 mitochondrial SNPs (mtSNPs), capturing four complexes of the mitochondrial OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,723 breast cancer cases and 3,260 controls from the Multiethnic Cohort Study.
resultsWe examined the collective set of 314 mtSNPs as well as subsets of mtSNPs grouped by mitochondrial OXPHOS pathway, complexes, and genes, using the sequence kernel association test and adjusting for age, sex, and principal components of global ancestry. We also tested haplogroup associations using unconditional logistic regression and adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. No significant mitochondrial OXPHOS pathway, gene, and haplogroup associations were observed in African Americans, Asian Americans, Latinos, and Native Hawaiians. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with breast cancer risk (P = 0.017, q = 0.102). In mtSNP-subset analysis, the gene MT-CO2 (P = 0.001, q = 0.09) in Complex IV (cytochrome c oxidase) and MT-ND2 (P = 0.004, q = 0.19) in Complex I (NADH dehydrogenase (ubiquinone)) were significantly associated with breast cancer risk.
conclusionsIn summary, our findings suggest that collective mitochondrial genetic variation and particularly in the MT-CO2 and MT-ND2 may play a role in breast cancer risk among European Americans. Further replication is warranted in larger populations and future studies should evaluate the contribution of mitochondrial proteins encoded by both the nuclear and mitochondrial genomes to breast cancer risk.
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