Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms
Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms
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DOI：
10.1038/s41408-020-00356-5
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发表时间：
2020-09-01
影响因子：
12.8
通讯作者：
Campa, Daniele
中科院分区：
文献类型：
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作者：
Giaccherini, Matteo;Macauda, Angelica;Campa, Daniele
已发现白细胞中测量的端粒长度（LTL）与发展几种癌症类型的风险相关，包括骨髓增生性肿瘤（MPN）。LTL在遗传上由至少11个先前显示影响LTL的SNP决定。它们在评分中的组合已被用作测量LTL的遗传工具，并评估LTL与几种癌症类型风险之间的因果关系。我们在一项欧洲多中心病例对照研究中，首次对480名MPN患者和909名健康对照者进行了“teloscore”测试。我们发现，遗传决定的端粒较长的患者发生MPN的风险增加（OR = 1.82，95%CI 1.24- 2.68，P = 2.21 x 10（-3），比较端粒分布的最高和最低五分位数）。通过对这些SNPs的单独分析，我们证实了TERT-rs 2736100-C等位基因与MPN发病风险增加之间的关联，我们还报道了OBFC 1-rs 9420907-C变异与MPN发病风险增加之间的新关联（OR等位基因= 1.43; 95%CI 1.15-1.77;P = 1.35 x 10（-3））。与用端粒评分获得的结果一致，两个风险等位基因也与较长的LTL相关。总之，我们的研究结果表明，基因决定的较长的端粒可能是MPN发展的风险标志。
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 x 10(-3), comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association betweenTERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of theOBFC1-rs9420907-C variant with higher MPN risk (ORallelic = 1.43; 95% CI 1.15-1.77;P = 1.35 x 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.