Mitochondrial DNA variant interactions modify breast cancer risk.
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.
Covarrubias
Daniel
D
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX, 77030, USA.|Department of Statistics, Rice University, Houston, TX, 77005, USA.
Bai
Ren-Kui
RK
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX, 77030, USA.
Wong
Lee-Jun C
LC
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX, 77030, USA.
Leal
Suzanne M
SM
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX, 77030, USA. sleal@bcm.edu.
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D018570:Risk Assessment
D004272:DNA, Mitochondrial