The Relationship Between Altered Mitochondrial DNA Copy Number And Cancer Risk: A Meta-Analysis

Jia Mi,Xianglin Li,Shuang Liu,Liwei Zhang,Tianhui Ni,Geng Tian,Bin Wang

doi:10.1038/srep10039

Abstract

Currently, a comprehensive assessment between mitochondrial DNA (mtDNA) content and cancer risk is lacking. We designed this meta-analysis to test the hypothesis that altered mtDNA copy number might influence genetic susceptibility to some specific types of cancer. The processes of literature search, eligibility appraisal and data retrieval were independently completed in duplicate. The mtDNA copy number which was dichotomized or classified into tertiles was compared between cancer cases and controls. Twenty-six articles with 38 study groups were analyzed among 6682 cases and 9923 controls. When dichotomizing mtDNA copy number at the median value, there was an 11% increased cancer risk for carriers of high mtDNA content (P = 0.320). By cancer type, high mtDNA content was associated with an increased risk for lymphoma (OR = 1.76; P = 0.023) but a reduced risk for skeleton cancer (OR = 0.39; P = 0.001). Carriers of the 2nd and 3rd tertiles of mtDNA copy number had an 1.74-fold (P = 0.010) and 2.07-fold (P = 0.021) increased risk of lymphoma, respectively. By contrast, there was correspondingly a 56% (P < 0.001) and 80% (P < 0.001) reduced risk of skeleton cancer. Our findings suggested that elevated mtDNA content was associated with a higher risk for lymphoma, but a lower risk for skeleton cancer.

Highlights

Mitochondrial DNA is an extra-chromosomal circular, double-stranded, maternally-inherited DNA; it is 16.5 kb in length and encodes for 37 genes, including 2 rRNAs, 13 mRNAs and 22 tRNAs1
Through layers of identification and assessment, a total of 26 articles were qualified that examined the association of altered mitochondrial DNA (mtDNA) copy number with cancer risk[5,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]
Digestive cancer was examined in 11 study groups, respiratory cancer in 6 groups, urogenital cancer in 6 groups, head and neck cancer in 5 groups, lymphoma in 5 groups, breast cancer in 3 groups and skeleton cancer in 2 groups

Summary

Introduction

Mitochondrial DNA (mtDNA) is an extra-chromosomal circular, double-stranded, maternally-inherited DNA; it is 16.5 kb in length and encodes for 37 genes, including 2 rRNAs, 13 mRNAs and 22 tRNAs1. Somatic mtDNA mutations are frequently observed in many sites of human cancer[3,4], and it gives a reason to expect that high mtDNA copy number might be a logical biomarker implicated in the onset and evolution of carcinogenesis. Subsequent observations argued against this observation by showing that low mtDNA copy number appeared to be associated with an increased risk of renal cell carcinoma[6,7], leading to the existence of tumor site-specific heterogeneity. In medical literature a comprehensive assessment between mtDNA content and cancer risk far is lacking. To fill this gap in knowledge, we set up a systematic meta-analysis to test the hypothesis that altered mtDNA copy number might influence genetic susceptibility to some specific types of cancer. We tried to track potential sources of heterogeneity through subgroup and meta-regression analyses

Methods

Results

Conclusion