Mitochondrial Genetics in Gastric Cancer

Abstract

Gastric carcinoma, in India, is the second most prevalent cause of cancer-related death since most patients are asymptomatic until the disease progresses to advanced stages. Hence, there is a need for non-invasive and specific biomarkers for early screening and diagnosis. Human mitochondrial DNA (mtDNA) has 37 genes involved in oxidative phosphorylation pathway (OxPhos). There are several 100 to 1000 mitochondria in a human cell and each mitochondrion has two to 10 copies of mtDNA. There is a significant association between the mtDNA copy number and an increase in risk of various cancers. There is also a relation between the changes in the sequence of mtDNA in genes, such as MT-CYB, MT-ATP6 and gastric cancer, according to which the tumor cells switch to aerobic glycolysis for ATP production even in the presence of oxygen due to Warburg effect. Multiple factors have an adverse effect on mitochondrial gene expression and impairs the OxPhos pathway due to lack of sophisticated DNA repair mechanism in mitochondria. Techniques, such as Next Generation Sequencing and Whole Genome Sequencing, are capable of early detection of copy number variants and mtDNA mutations in blood sample essential for better prognosis of gastric cancer. Through the course of this study, various reports of a correlation between mtDNA damage and gastric cancer were analyzed and it was found that the increasing evidence of the role of mtDNA and its copy number in cancer indicates its significance as a potential biomarker for GC.