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 × gene interactions will give a greater knowledge of disease etiology and aid in interpreting a woman’s risk of developing breast cancer.
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This study was supported in part by NIH grant CA10023 and Department of Defense US Army Breast Cancer Research Program, DAMD17-01-1-0258.
D. Covarrubias and R.-K. Bai contributed equally to this article.
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Covarrubias, D., Bai, R., Wong, L.C. et al. Mitochondrial DNA variant interactions modify breast cancer risk. J Hum Genet 53, 924–928 (2008) doi:10.1007/s10038-008-0331-x
- Mitochondrial DNA
- Breast cancer
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