Mitochondrial DNA polymorphisms, its copy number change and outcome in colorectal cancer

Mohideen, Asan Meera Sahib Haja and Dicks, Elizabeth and Parfrey, Patrick S. and Green, Roger C. and Savas, Sevtap (2015) Mitochondrial DNA polymorphisms, its copy number change and outcome in colorectal cancer. BMC Research Notes, 8 (272). ISSN 1756-0500

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Abstract

Background Mitochondrion is a small organelle inside the eukaryotic cells. It has its own genome (mtDNA) and encodes for proteins that are critical for energy production and cellular metabolism. Mitochondrial dysfunctions have been implicated in cancer progression and may be related to poor prognosis in cancer patients. In this study we hypothesized that genetic variations in mtDNA are associated with clinical outcome in colorectal cancer patients. Methods We tested the associations of six mtDNA polymorphisms [MitoT479C, MitoT491C, MitoT10035C, MitoA13781G, 10398 (A/G), and 16189 (T/C)] and the mtDNA copy number change with overall survival (OS) and disease-free survival (DFS) times. Two mtDNA polymorphisms were genotyped using the TaqMan® SNP genotyping technique and the genotypes for the remaining four mtDNA polymorphisms were obtained by the Illumina® HumanOmni1-Quad genome wide SNP genotyping platform in 536 patients. The mtDNA copy number change (in tumor tissues with respect to non-tumor tissues) was estimated using the quantitative real time polymerase chain reaction for 274 patients. Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method. Results In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively. However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort. Conclusions Our results suggest that the mitochondrial genetic markers investigated in this study are not associated with outcome in colorectal cancer.

Item Type: Article
URI: http://research.library.mun.ca/id/eprint/11806
Item ID: 11806
Additional Information: Memorial University Open Access Author's Fund
Keywords: Mitochondrial DNA, Colorectal cancer, Prognosis, Polymorphisms, Mitochondrial, DNA copy number change
Department(s): Medicine, Faculty of
Date: 27 June 2015
Date Type: Publication
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