Mitochondrial Cytochrome c Oxidase subunit 1 Sequence Variation in Prostate Cancer

Mitochondrial DNA (mtDNA) gene mutations have been described in nearly every adult solid neoplasm including prostate cancer. There are marked racial differences in specific inherited mutations within the cytochrome c oxidase subunit 1 (COI) gene in individuals with prostate cancer (PCa). The purpose of this study was to identify the variation in COI gene sequence in prostate cancer patients and to compare the mutations in African and Caucasian Americans.

We sequenced the COI gene in DNA derived from peripheral blood in 482 prostate cancer patients and 189 controls. All bases that differed from the revised Cambridge Reference Sequence (rCRS) were classified as either silent (non-amino acid altering) or missense (amino acid altering) and the compiled alterations were then compared between races and published reports of mutations in this gene in both Caucasian and African-Americans.

We found inherited mtDNA COI missense variants in 8.8% of Caucasian prostate cancer patients (vs. 0.0% controls) and 72.8 % of African-American prostate cancer patients (vs. 64.3% controls) A total of 144 COI variants were identified, of which 30 were missense mutations. Of 482 PCa patients, 116 (24.1%) had one or more missense mutations. Further evaluation of this gene and these mutations may allow for the identification of genetically at-risk populations. The high rate of COI mutations in African-Americans may account for some of the racial disparity observed in prostate cancer.