The Mitochondrial DNA Northeast Asia CZD Haplogroup Is Associated with Good Disease-Free Survival among Male Oral Squamous Cell Carcinoma Patients

Reprogramming of energy metabolism in cancer cells has been directly/indirectly linked to mitochondria and mitochondrial functional defects and these changes seem to contribute to the development and progression of cancer. Studies have indicated that mitochondrial DNA haplogroups are associated with risk in relation to various diseases including cancer. However, few studies have examined the effect of haplogroups on cancer prognosis outcome. In order to explore the role of haplogroups on oral squamous cell carcinoma (OSCC) prognosis, the mitochondrial genomes of 300 male OSCC patients were comprehensively analyzed by direct sequencing. They were then haplotyped and grouped into four major geographic haplogroups, namely the East Asia AN, Southeast Asia RBF, East Asia MGE and Northeast Asia CZD groups. The Kaplan-Meier plot analysis indicated that individuals who were members of the CZD haplogroup showed a significant association with better disease-free survival (DFS) than the other three haplogroups and this phenomenon still existed after adjusting for tumor stage, differentiation and age at diagnosis (hazard ratio=0.55; 95% CI=0.36-0.84). In addition, an interaction between membership of the RBF haplogroup and radiotherapy/chemo-radiotherapy in DFS was also identified. The results strongly support the hypothesis that an individual's haplogroup, by defining their genomic background, plays an important role in tumor behavior and mitochondrially-targeted anticancer drugs are promising future therapeutic approaches.