Shen Jie, Wan Jie, Huff Chad, Fang Shenying, Lee Jeffrey E, Zhao Hua
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pigment Cell Melanoma Res. 2016 May;29(3):372-8. doi: 10.1111/pcmr.12474.
The 4977-base pair common deletion DmtDNA4977 is the most frequently observed mitochondrial DNA mutation in human tissues. Because mitochondrial DNA mutations are mainly caused by reactive oxygen species (ROS), and given that oxidative stress plays an important role in melanoma carcinogenesis, the investigation of DmtDNA4977 may be particularly relevant to the development of melanoma. In this study, we compared DmtDNA4977 levels in blood leukocytes from 206 melanoma patients and 219 healthy controls. Overall, melanoma cases had significantly higher levels of DmtDNA4977 than healthy controls (median: 0.60 vs 0.20, P = 0.008). The difference was evident among individuals who were older than 47 yrs, women, and had pigmentation risk factors (e.g., blond or red hair, blue eye, fair skin, light, or none tanning ability after prolonged sun exposure, and freckling in the sun as a child). The difference was also evident among those who had at least one lifetime sunburn with blistering and had no reported use of a sunlamp. Interestingly, among controls, DmtDNA4977 levels differed by phenotypic index and reported use of a sunlamp. In the risk assessment, increased levels of DmtDNA4977 were associated with a 1.23-fold increased risk of melanoma (odds ratio (OR): 1.23, 95% confidence interval (90% CI): 1.01, 1.50). A significant dose-response relationship was observed in quartile analysis (P = 0.001). In summary, our study suggests that high levels of DmtDNA4977 in blood leukocytes are associated with increased risk of melanoma and that association is affected by both pigmentation and personal history of sun exposure.
4977个碱基对的常见缺失DmtDNA4977是人类组织中最常观察到的线粒体DNA突变。由于线粒体DNA突变主要由活性氧（ROS）引起，并且鉴于氧化应激在黑色素瘤致癌过程中起重要作用，对DmtDNA4977的研究可能与黑色素瘤的发生发展特别相关。在本研究中，我们比较了206例黑色素瘤患者和219例健康对照者血液白细胞中的DmtDNA4977水平。总体而言，黑色素瘤患者的DmtDNA4977水平显著高于健康对照者（中位数：0.60对0.20，P = 0.008）。在年龄大于47岁、女性以及有色素沉着风险因素（如金发或红发、蓝眼睛、白皙皮肤、长时间日晒后晒黑能力弱或无晒黑能力以及儿童期阳光下雀斑）的个体中，这种差异很明显。在至少有一次晒伤起泡且未报告使用过太阳灯的个体中，差异也很明显。有趣的是，在对照者中，DmtDNA4977水平因表型指数和报告的太阳灯使用情况而异。在风险评估中，DmtDNA4977水平升高与黑色素瘤风险增加1.23倍相关（优势比（OR）：1.23，95%置信区间（90%CI）：1.01，1.50）。在四分位数分析中观察到显著的剂量反应关系（P = 0.001）。总之，我们的研究表明，血液白细胞中高水平的DmtDNA4977与黑色素瘤风险增加相关，并且这种关联受色素沉着和个人日晒史的影响。
