Association of mitochondrial copy number variation and T16189C polymorphism with colorectal cancer in North Indian population

Abstract

Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58-154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3-6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.

A Pipeline for Faecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR

“…Mitochondria are responsible for ATP (energy) generation, reactive oxygen species generation and detoxification, and other essential functions in the cell 38 . Mitochondrial copy number alterations have been linked to autism 39,40 and multiple types of cancer including breast cancer 41,42 , bladder cancer 42 , kidney cancer 42 , and colon cancer 43,44 . Thus for example, our mitochondrial DNA quantification assays could be adapted to measure such mt copy number alterations in biofluids (e.g., urine, blood, cyst fluid, and cerebrospinal fluid) in cancer patients as a biomarker approach.…”

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer

“…These regions are associated with mitochondrial genome instability [113,114]. Multiple other hotspots have been identified in the D-loop region including the T16189C polymorphism in endometrial cancer [115], rectal cancer [116], melanoma [94], and prostate cancer [117,118]. Interestingly, this SNP has been associated with metabolic disease and type II diabetes [119,120], further supporting a linkage between mitochondrial polymorphisms, metabolism and neoplastic development.…”

Mitogenome germline mutations and colorectal cancer risk in Polish population

“…Previous studies suggested that certain polymorphic mtDNA positions may be associated with increased risk of colorectal cancer in Iranian, Indian or European Americans [16][17][18][19][20]. In contrast, the studies performed on other ethnic groups (e.g.…”

“…As mtDNA allele and haplogroup frequencies highly vary between different populations, it is important to evaluate the genetic risk of cancer in a specific ethnic context. To date, several studies have been carried out to investigate the associations of single mitochondrial DNA polymorphic sites (SNPs) with colorectal cancer in different ethnic groups [15][16][17][18][19][20]. The analysed SNPs were hotspots or positions diagnostic for major haplogroups.…”