So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer cells is still unknown, and neither is their significance in carcinogenesis. Indeed, it remains debatable whether mtDNA mutations are "drivers" or "passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from normal and cancer tissues of 100 colorectal cancer patients. Minority variant mutations were detected at the 1% level. We showed that somatic mutations frequently occur in colorectal cancer cells (75%) and are randomly distributed across the mitochondrial genome. Mutational signatures of somatic mitogenome mutations suggest that they might arise through nucleotide deamination due to oxidative stress. The majority of somatic mutations localized within the coding region (in positions not known from the human phylogeny) and was potentially pathogenic to cell metabolism. Further analysis suggested that the relaxation of negative selection in the mitogenomes of colorectal cancer cells may allow accumulation of somatic mutations. Thus, a shift in glucose metabolism from oxidative phosphorylation to glycolysis may create advantageous conditions for accumulation of mtDNA mutations. Considering the fact that the presence of somatic mtDNA mutations was not associated with any clinicopathological features, we suggested that mtDNA somatic mutations are "passengers" rather than the cause of colorectal carcinogenesis.

No abstract

Aim of the studyColorectal cancer (CRC) is one of the leading cause of death in European population. It progresses without any symptoms in the early stages or those clinical symptoms are very discrete. The aim of this study was a retrospective analysis of treatment outcomes in patients with colorectal cancer complicated with intestinal perforation.Material and methodsA retrospective analysis of patients urgently operated upon in our Division of General Surgery, because of large intestine perforation, from February 1993 to February 2013 has been made. Results were compared with a group of patients undergoing the elective surgery for colorectal cancer in the same time and Division.ResultsIntestinal perforation occurred more often in males (6.52% vs. 6.03%), patients with mucous component in histopathological examination (9.09% vs. 6.01%) and with clinicaly advanced CRC. Patients treated because of perforation had a five-fold higher 30 day mortality rate (9.09% vs. 1.83%), however long-term survival did not differ significantly in both groups. After resectional surgery in 874 patients an intestinal anastomosis was made. Anastomotic leakage was present in 23 (2.6%) patients. This complication occurred six-fold more frequently in a group of patients operated upon because of intestinal perforation (12.20% vs. 2.16%).ConclusionsIn patients with CRC complicated with perforation of the colon in a 30-day observation significantly higher rate of complications and mortality was shown, whereas there was no difference in distant survival rates.