Mitochondrial DNA variant interactions modify breast cancer risk

J Hum Genet. 2008;53(10):924-928. doi: 10.1007/s10038-008-0331-x. Epub 2008 Aug 19.


Interactions between mitochondrial deoxyribonucleic acid (mtDNA) variants and the risk of developing breast cancer were investigated using DNA samples collected from non-Jewish European American breast cancer patients and ethnically age-matched female controls. Logistic regression was used to evaluate two-way interactions between 17 mtDNA variants. To control for multiple testing, empirical P values were calculated using permutation. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to measure the contribution of variants in modifying the risk of developing breast cancer. A highly significant interaction was identified between variants 12308G and 10398G (empirical P value = 0.0028), with results suggesting these variants increase the risk of a woman developing breast cancer (OR = 3.03; 95% CI 1.53-6.11). Nominal significant P values were also observed for interactions between mtDNA variants 709A and 16189C; 4216C and 10398G; 4216C and 16189C; 10398G and 16159C; 13368A and 16189C; and 14766T and 16519C. However, after adjusting for multiple testing, the P values did not remain significant. Although it is important to elucidate the main effect of mtDNA variants on the risk of developing breast cancer, understanding gene x gene interactions will give a greater knowledge of disease etiology and aid in interpreting a woman's risk of developing breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Case-Control Studies
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Assessment


  • DNA, Mitochondrial