Genetically determined telomere length and multiple myeloma risk and outcome.
Genetically determined telomere length and multiple myeloma risk and outcome.
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DOI：
10.1038/s41408-021-00462-y
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发表时间：
2021-04-14
影响因子：
12.8
通讯作者：
Campa D
中科院分区：
文献类型：
--
作者：
Giaccherini M;Macauda A;Orciuolo E;Rymko M;Gruenpeter K;Dumontet C;Raźny M;Moreno V;Buda G;Beider K;Varkonyi J;Avet-Loiseau H;Martinez-Lopez J;Marques H;Watek M;Sarasquete ME;Andersen V;Karlin L;Suska A;Kruszewski M;Abildgaard N;Dudziński M;Butrym A;Nagler A;Vangsted AJ;Kadar K;Waldemar T;Jamroziak K;Jacobsen SEH;Ebbesen LH;Taszner M;Mazur G;Lesueur F;Pelosini M;Garcia-Sanz R;Jurczyszyn A;Demangel D;Reis RM;Iskierka-Jażdżewska E;Markiewicz M;Gemignani F;Subocz E;Zawirska D;Druzd-Sitek A;Stępień A;Alonso MH;Sainz J;Canzian F;Campa D
端粒参与细胞生长，染色体稳定性和正确分离子细胞等过程。已在不同癌症类型（包括多发性骨髓瘤（MM））中研究了白细胞（LTL）中测量的端粒长度。然而，由于样本处理和研究设计（回顾性与前瞻性），LTL测量容易出现异质性。LTL由基因决定;全基因组关联研究确定了11个SNP，这些SNP组合在一个评分中，可以用作测量LTL和评估其与MM风险的关联的遗传工具。这种方法已经成功地尝试在各种癌症类型，但从来没有在MM。我们测试了“teloscore”在2407 MM患者和1741控制从国际多发性骨髓瘤rESEarch（IMMeNSE）财团。我们观察到基因决定的端粒长度（gdTL）较长的风险增加（OR = 1.69; 95% CI 1.36-2.11;得分最高与最低五分位数的P = 2.97 × 10−6）。此外，在1376例MM患者的亚组中，我们测试了终末评分与MM患者生存率之间的关系，观察到较长gdTL的预后优于较短gdTL（HR = 0.93; 95%CI 0.86-0.99; P = 0.049）。总之，我们报告了令人信服的证据，即较长的gdTL是MM风险的风险标志物，并且它可能与MM生存率的增加有关。
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.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
12.8
作者：
Giaccherini, Matteo;Macauda, Angelica;Campa, Daniele
通讯作者：
Campa, Daniele
影响因子：
2.6
作者：
Campa, Daniele;Martino, Alessandro;Canzian, Federico
通讯作者：
Canzian, Federico
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M