Sequence variation in the mitochondrial gene cytochrome c oxidase subunit I and prostate cancer in African American men

• Type of Material: Article
• Authors: Anna M. Ray, University of Michigan; Kimberly A. Zuhlke, University of Michigan; Albert M. Levin, University of Michigan; Julie A. Douglas, University of Michigan; Kathleen A. Cooney, University of Michigan; John A Petros, Emory University
• Language: English
• Date: 2009-06-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Wiley-Liss, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/pros.20943/abstract
• Title of Journal or Parent Work: Prostate
• ISSN: 0270-4137
• Volume: 69
• Issue: 9
• Start Page: 956
• End Page: 960
• Grant/Funding Information: Funding for this project was provided by NIH SPORE P50 CA69568, the University of Michigan Comprehensive Cancer Center, and the University of Michigan Medical School Department of Urology.
• Keywords: SNP; COI; association; prostate cancer
• Research Categories: Biology, Genetics; Health Sciences, Oncology

Abstract

Background: Previous studies have found associations between mitochondrial DNA (mtDNA) mutations and several cancer types. Recently, we found that mutations in the mtDNA gene cytochrome c oxidase subunit 1 (COI) were both linked to and associated with prostate cancer (PCa) in Caucasian men. Here we examine the association between COI mutations and PCa in African American men. Methods: The entire COI gene was directly sequenced in 132 PCa cases and 135 controls from the Flint Men’s Health Study, a community-based sample of African American men with and without PCa. Associations between all variants and PCa were evaluated. Results: We identified 102 COI single nucleotide polymorphisms (SNPs), including 15 missense variants. Overall, the presence of one or more COI missense variants was not significantly associated with PCa. Individually, two SNPs (T6221C and T7389C) were significantly associated with prostate cancer (P < 0.05) and in strong linkage disequilibrium with each other (r2 > 0.6). Conclusions: Of the two significantly associated SNPs, one is a synonymous substitution and the other is part of the African-specific mitochondrial haplogroup (L). Additional research will be needed to determine the clinical relevance of these associations in African populations.