Covarrubias Daniel, Bai Ren-Kui, Wong Lee-Jun C, Leal Suzanne M
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.
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.
利用从非犹太裔欧美乳腺癌患者和种族、年龄匹配的女性对照中收集的DNA样本，研究了线粒体脱氧核糖核酸（mtDNA）变异与患乳腺癌风险之间的相互作用。采用逻辑回归评估17种mtDNA变异之间的双向相互作用。为控制多重检验，使用排列法计算经验P值。计算优势比（OR）和相应的95%置信区间（CI），以衡量变异对改变患乳腺癌风险的贡献。在变异12308G和10398G之间发现了高度显著的相互作用（经验P值 = 0.0028），结果表明这些变异会增加女性患乳腺癌的风险（OR = 3.03；95% CI 1.53 - 6.11）。对于mtDNA变异709A和16189C；4216C和10398G；4216C和16189C；10398G和16159C；13368A和16189C；以及14766T和16519C之间的相互作用，也观察到了名义上显著的P值。然而，在调整多重检验后，P值不再显著。虽然阐明mtDNA变异对患乳腺癌风险的主要影响很重要，但了解基因×基因相互作用将更深入地了解疾病病因，并有助于解释女性患乳腺癌的风险。
