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

BMC Research Notes

Sevtap Savas¹  Roger Green³  Patrick Parfrey²  Elizabeth Dicks²  Asan Meera Sahib Haja Mohideen³ 

[1] Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada;Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada;Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John’s A1B 3V6, NL, Canada

关键词: Mitochondrial DNA copy number change;    Polymorphisms;    Prognosis;    Colorectal cancer;    Mitochondrial DNA;   

Others  :  1231642
DOI  :  10.1186/s13104-015-1250-5

 received in 2015-03-23, accepted in 2015-06-17,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Haja Mohideen et al.

【 图 表 】

Figure1.

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