No association between the mitochondrial genome and prostate cancer risk: The Multiethnic Cohort
A partir des données d'une cohorte multi-ethnique incluant 4 086 cas et 3 698 témoins, cette étude évalue l'association entre 350 polymorphismes à simple nucléotide de l'ADN mitochondrial et le risque de cancer de la prostate
Background: Mitochondria are involved in many processes that are central to the life and death of a cell. Oxidative phosphorylation (OXPHOS), in particular, is known to be altered in carcinogenesis, leading to an increase in the production of reactive oxidative species and glycolysis, one of the hallmarks of cancer cells. Because of this, genetic variation in the mitochondrial genome, which encodes for part of the OXPHOS pathway, has been suggested to play a role in many cancers, including prostate cancer. Methods: We comprehensively examined the role of the mitochondrial genome and prostate cancer risk in 4,086 prostate cancer cases and 3,698 controls from the Multiethnic Cohort, testing 350 mitochondrial SNPs (mtSNPs) in five racial/ethnic populations-Africans, Asian Americans, Europeans, Latinos, and Native Hawaiians. Logistic regression was conducted to examine single mitochondrial SNP and haplogroup associations. The sequence kernel association test was conducted for gene and pathway analysis. Results: Eleven mtSNPs and haplogroup N were nominally associated with overall prostate cancer risk at P<0.05. The mitochondrial DNA encoded OXPHOS pathway, complexes, and genes were not associated with prostate cancer risk. No significant associations were identified after multiple testing correction (all FDR q>0.20). Conclusions: The mitochondrial genome was not associated with prostate cancer risk in our study of 7,784 subjects from the Multiethnic Cohort. Impact: Our comprehensive study does not support the role of the mitochondrial genome in the risk of prostate cancer.