Association of mitochondrial displacement loop polymorphisms with risk of colorectal cancer in south Indian population

Abstract

Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species. In the present study, we sequenced the entire mitochondrial D-loop region (1124 bp) of colorectal cancer (CRC) patients (n = 174) and controls (n = 170) of south Indian origin to identify significant mutations/polymorphisms. Our results showed 152 polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (54.6%) than in II (45.4%) of D-loop region. The frequencies of 310‘C’ insertion (p = 0.0078), T16189C (p = 0.0097) variants and 310‘C’ins/16189C haplotype (p = 0.0029) were significantly higher in cases than in controls. Furthermore, strong linkage disequilibrium was observed between nucleotide position 310 and 16189 in cases (D'=0.68) as compared with controls (D'=0.27). In conclusion, mitochondrial D-loop sequence alterations may constitute inherent risk factor for CRC.

Keywords:

• Colorectal cancer
• d-loop
• haplotype
• mitochondria
• polymorphism

Acknowledgements

The authors deeply thank all the medical staff and study subjects involved in this study. Dr. PS Rao sincerely acknowledges Dr. Sreeram Sateesh, Professor and Head, Dept of General Surgery, NMCH for his consistent help in sample collection and fruitful discussions at all stages of the manuscript preparation.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding information

This work received no financial support.