The saga of the many studies wrongly associating mitochondrial DNA with breast cancer

BMC Cancer. 2014 Sep 9:14:659. doi: 10.1186/1471-2407-14-659.


Background: A large body of genetic research has focused on the potential role that mitochondrial DNA (mtDNA) variants might play on the predisposition to common and complex (multi-factorial) diseases. It has been argued however that many of these studies could be inconclusive due to artifacts related to genotyping errors or inadequate design.

Methods: Analyses of the data published in case-control breast cancer association studies have been performed using a phylogenetic-based approach. Variation observed in these studies has been interpreted in the light of data available on public resources, which now include over >27,000 complete mitochondrial sequences and the worldwide phylogeny determined by these mitogenomes. Complementary analyses were carried out using public datasets of partial mtDNA sequences, mainly corresponding to control-region segments.

Results: By way of example, we show here another kind of fallacy in these medical studies, namely, the phenomenon of SNP-SNP interaction wrongly applied to haploid data in a breast cancer study. We also reassessed the mutually conflicting studies suggesting some functional role of the non-synonymous polymorphism m.10398A>G (ND3 subunit of mitochondrial complex I) in breast cancer. In some studies, control groups were employed that showed an extremely odd haplogroup frequency spectrum compared to comparable information from much larger databases. Moreover, the use of inappropriate statistics signaled spurious "significance" in several instances.

Conclusions: Every case-control study should come under scrutiny in regard to the plausibility of the control-group data presented and appropriateness of the statistical methods employed; and this is best done before potential publication.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • DNA, Mitochondrial*
  • Epistasis, Genetic
  • Female
  • Genetic Association Studies
  • Haplotypes
  • Humans
  • Polymorphism, Single Nucleotide
  • Population Groups / genetics
  • Publication Bias
  • Risk


  • DNA, Mitochondrial