文章：

与端粒长度相关的遗传多态性及患骨髓增殖性肿瘤风险

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

原文发布日期：2020-09-01

DOI: 10.1038/s41408-020-00356-5

类型: Article

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英文摘要：

Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic = 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.
 

摘要翻译： 

白细胞端粒长度（LTL）已被发现与包括骨髓增殖性肿瘤（MPNs）在内的多种癌症发病风险相关。LTL由至少11个先前被证实可影响端粒长度的单核苷酸多态性（SNPs）所遗传决定。这些SNPs组合形成的评分体系已被用作遗传工具来测量LTL，并评估LTL与多种癌症风险之间的因果关系。我们首次在欧洲多中心病例对照研究中，对480名MPN患者和909名健康对照者进行了“端粒评分”检测。研究发现，遗传决定的较长端粒会增加MPN发病风险（比较端粒评分分布最高与最低五分位数组：OR=1.82，95% CI 1.24-2.68，P=2.21×10−3）。通过单独分析SNPs，我们证实了TERT-rs2736100-C等位基因与MPN风险增加的相关性，并首次报道OBFC1-rs9420907-C变异与较高MPN风险存在新关联（等位基因OR=1.43；95% CI 1.15-1.77；P=1.35×10−3）。与端粒评分结果一致的是，这两个风险等位基因同样与较长的LTL相关。本研究结果表明，遗传决定的较长端粒可能成为MPN发展的风险标志物。

原文链接：

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms