Ye Chuanzhong, Gao Yu-Tang, Wen Wanqing, Breyer Joan P, Shu Xiao Ou, Smith Jeffrey R, Zheng Wei, Cai Qiuyin
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine and Vanderbilt Ingram-Cancer Center, Nashville, TN 37232-2400, USA.
Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2117-22. doi: 10.1158/1055-9965.EPI-07-2798.
Mitochondrial genome alternations may be involved in carcinogenesis. The noncoding region of the mitochondrial DNA (mtDNA) displacement loop (D-loop) has emerged as a mutational hotspot. Using data from a population-based case-control study conducted among Chinese women in Shanghai, we evaluated associations of breast cancer risk and survival with the mtDNA D-loop (CA)(n) dinucleotide repeat polymorphism. Included in the study were 1,058 cases and 1,129 age frequency-matched community controls that participated in the Shanghai Breast Cancer Study between 1996 and 1998. Breast cancer patients were followed to determine intervals of overall survival and disease-free survival. Overall, there was no association between the mtDNA D-loop (CA)(n) repeat polymorphism and breast cancer risk. Patients with multiple alleles of the mtDNA D-loop (CA)(n) polymorphism (heteroplasmy) had significantly poorer disease-free survival than those with one allele of the mtDNA D-loop (CA)(n) polymorphism (hazard ratio 1.62; 95% confidence interval, 1.16-2.26). These results suggest that the mtDNA D-loop (CA)(n) repeat polymorphism may be associated with breast cancer survival. Additional studies with a larger sample size are warranted.
线粒体基因组改变可能参与致癌过程。线粒体DNA（mtDNA）置换环（D-loop）的非编码区已成为一个突变热点。利用在上海中国女性中开展的一项基于人群的病例对照研究的数据，我们评估了mtDNA D-loop（CA）（n）二核苷酸重复多态性与乳腺癌风险及生存的关联。该研究纳入了1996年至1998年间参与上海乳腺癌研究的1058例病例和1129例年龄频率匹配的社区对照。对乳腺癌患者进行随访以确定总生存和无病生存时间。总体而言，mtDNA D-loop（CA）（n）重复多态性与乳腺癌风险之间无关联。mtDNA D-loop（CA）（n）多态性具有多个等位基因（异质性）的患者无病生存显著差于mtDNA D-loop（CA）（n）多态性具有一个等位基因的患者（风险比1.62；95%置信区间，1.16 - 2.26）。这些结果提示，mtDNA D-loop（CA）（n）重复多态性可能与乳腺癌生存相关。需要开展更大样本量的进一步研究。
