Nie Qian, Zhang Wenzhe, Lin Songping, Huang Meng, Li Yan, Qiu Yibin, Li Jing, Chen Xiaobin, Wang Yali, Tong Xin, Wu Jinqiao, He Peng, Cai Qindong, Chen Lili, Chen Minyan, Guo Wenhui, Lin Yuxiang, Yu Liuwen, Hou Jialin, Cai Weifeng, Chen Hanxi, Wang Chuan, Fu Fangmeng
Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Cancer Sci. 2024 Dec;115(12):4064-4073. doi: 10.1111/cas.16353. Epub 2024 Oct 14.
Mitochondrial DNA (mtDNA) variations affect the efficiency of the electron transport chain and production of reactive oxygen species, contributing to carcinogenesis. The D-loop region of mtDNA has emerged as a variation hotspot region in human neoplasia; however, the potential contribution of these variations in breast cancer risk prediction remains unknown. We investigated the relationship between germline single nucleotide polymorphisms (SNPs) in the entire D-loop region and breast cancer risk in Chinese women. Peripheral blood-isolated mtDNA from 2329 patients with breast cancer and 2328 cancer-free controls was examined for SNPs. In the combined cohort, we used traditional risk factors, susceptibility germline polymorphisms, and logistic regression analysis to evaluate the predictive value of susceptibility variants for breast cancer risk. We calculated the area under the receiver operating characteristic curve (AUC) as a measure. We also measured the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Individual polymorphisms SNP573 were significantly associated with breast cancer risk in both the discovery and validation cohorts. In the combined cohort, the AUC of the traditional risk factors was 64.3%; after adding susceptibility variants, the AUC was 64.9% (DeLong test, p = 0.007). 8-OHdG levels were significantly higher in patients with breast cancer than in controls and higher in individuals with SNP573 than in those negative for this variation. Overall, oxidative stress might be associated with the risk of breast cancer, and SNP573 might be associated with oxidative stress. Our results indicate the risk potential of polymorphisms in the D-loop region in breast cancer in Southern China.
线粒体DNA（mtDNA）变异会影响电子传递链的效率和活性氧的产生，从而促进肿瘤发生。mtDNA的D环区域已成为人类肿瘤形成中的一个变异热点区域；然而，这些变异在乳腺癌风险预测中的潜在作用尚不清楚。我们研究了中国女性整个D环区域的种系单核苷酸多态性（SNP）与乳腺癌风险之间的关系。对2329例乳腺癌患者和2328例无癌对照外周血分离的mtDNA进行SNP检测。在合并队列中，我们使用传统风险因素、易感性种系多态性和逻辑回归分析来评估易感性变异对乳腺癌风险的预测价值。我们计算受试者工作特征曲线下面积（AUC）作为衡量指标。我们还测量了8-羟基-2'-脱氧鸟苷（8-OHdG）的含量。在发现队列和验证队列中，个体多态性SNP573均与乳腺癌风险显著相关。在合并队列中，传统风险因素的AUC为64.3%；加入易感性变异后，AUC为64.9%（德龙检验，p = 0.007）。乳腺癌患者的8-OHdG水平显著高于对照组，携带SNP573的个体高于该变异阴性个体。总体而言，氧化应激可能与乳腺癌风险相关，而SNP573可能与氧化应激相关。我们的结果表明中国南方乳腺癌中D环区域多态性的风险潜力。
