Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.
Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.
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端粒长度较短会增加冯·希佩尔-林道病患者与年龄相关的肿瘤风险
DOI：
10.1002/cam4.1134
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发表时间：
2017-09
期刊：
影响因子：
4
通讯作者：
Gong K
中科院分区：
文献类型：
--
作者：
Wang JY;Peng SH;Ning XH;Li T;Liu SJ;Liu JY;Hong BA;Qi NN;Peng X;Zhou BW;Zhang JF;Cai L;Gong K
Von Hippel-Lindau病(VHL)是一种罕见的常染色体显性遗传性癌症综合征，由VHL基因改变引起。患者易患嗜铬细胞瘤以及中枢神经系统、肾脏、胰腺和视网膜的实性或囊性肿瘤。VHL家系之间和家系内的器官受累和肿瘤发病年龄存在显著的表型异质性。然而，还没有发现可靠的标记物来预测VHL患者年龄相关的肿瘤风险。我们的研究纳入了一个由300名VHL患者和92名健康家系组成的中国队列。对184例患者和所有获得基因组DNA样本的对照进行了血液相对端粒长度的测量。使用Kaplan-Meier图和Cox回归分析来评估五种主要的VHL相关肿瘤的年龄相关风险。在中国队列和英国队列中观察到临床表型的差异。VHL患者端粒长度明显短于正常家系(P<0.0183)，且端粒长度与5种主要肿瘤的发病年龄呈正相关。此外，端粒较短组(年龄调整后的端粒长度≤为0.44)患者患病毒性霍奇金淋巴瘤相关的中枢神经系统血管母细胞瘤(HR：1.879，P=0.0.004)、肾癌(HR：2.126，P=0.0.002)和胰腺囊肿和神经内分泌肿瘤(HR：2.093，P=0.001)的年龄相关风险较高。这些结果表明，血液端粒长度缩短是VHL患者年龄相关肿瘤风险的一个新的生物标志物，这将对遗传咨询和未来关于端粒缩短在VHL相关肿瘤发病机制中的作用的研究至关重要。
Von Hippel‐Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age‐related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age‐related risks for the five major VHL‐associated tumors were evaluated using Kaplan–Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age‐adjusted telomere length ≤ 0.44) suffered higher age‐related risks for VHL‐associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age‐related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL‐associated tumors.
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影响因子：
3.9
作者：
Ong, Kai Ren;Woodward, Emma R.;Maher, Eamorm R.
通讯作者：
Maher, Eamorm R.
影响因子：
4
作者：
Maher, ER;Webster, AR;Moore, AT
通讯作者：
Moore, AT
影响因子：
3.9
作者：
Gallou, C;Chauveau, D;Béroud, C
通讯作者：
Béroud, C
影响因子：
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作者：
Perez-Cabornero, Lucia;Infante, Mar;Duran, Mercedes
通讯作者：
Duran, Mercedes
端粒缩短与中国 Von Hippel-Lindau 病家族的遗传预期相关。
影响因子：
11.2
作者：
Ning, Xiang-hui;Zhang, Ning;Gong, Kan
通讯作者：
Gong, Kan