文章：

遗传决定的端粒长度与多发性骨髓瘤的风险及预后

Genetically determined telomere length and multiple myeloma risk and outcome

原文发布日期：2021-04-14

DOI: 10.1038/s41408-021-00462-y

类型: Article

开放获取: 是

英文摘要：

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the “teloscore” in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36–2.11; P = 2.97 × 10−6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86–0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.
 

摘要翻译： 

端粒参与细胞生长、染色体稳定性以及向子细胞的正确分离等过程。白细胞端粒长度（LTL）已在多种癌症类型中得到研究，包括多发性骨髓瘤（MM）。然而，由于样本处理和研究设计（回顾性与前瞻性）的差异，LTL测量易受异质性影响。LTL由遗传因素决定；全基因组关联研究已鉴定出11个单核苷酸多态性（SNP），将其组合成评分可作为遗传工具用于测量LTL，并评估其与MM风险的关联。该方法已在多种癌症类型中成功尝试，但从未应用于MM。我们通过国际多发性骨髓瘤研究（IMMeNSE）联盟对2407例MM患者和1741例对照者进行了"端粒评分"测试。我们发现较长的遗传决定端粒长度（gdTL）会增加患病风险（评分最高与最低五分位相比：OR=1.69；95% CI 1.36–2.11；P=2.97×10−6）。此外，在1376例MM患者的亚组中，我们测试了端粒评分与患者生存期的关系，观察到较长gdTL比较短gdTL预后更好（HR=0.93；95% CI 0.86–0.99；P=0.049）。综上所述，我们提供了令人信服的证据，表明较长的gdTL是MM风险标志物，并可能参与延长MM患者的生存期。

原文链接：

Genetically determined telomere length and multiple myeloma risk and outcome