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长端粒的遗传易感性与黑色素瘤患者的死亡率增加相关:来自医院门诊和一般人群的 2101 名黑色素瘤患者的研究。

Genetic predisposition to long telomeres is associated with increased mortality after melanoma: A study of 2101 melanoma patients from hospital clinics and the general population.

机构信息

Department of Clinical Biochemistry, The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark.

出版信息

Pigment Cell Melanoma Res. 2021 Sep;34(5):946-954. doi: 10.1111/pcmr.12971. Epub 2021 May 7.

DOI:10.1111/pcmr.12971
PMID:33749133
Abstract

Whether there is an association between measured and genetically predicted telomere length and melanoma mortality is unclear. We tested the hypothesis that measured and genetically predicted telomere length is associated with mortality after a melanoma diagnosis. We followed 2,101 patients with melanoma from hospital clinics and the general population for risk of death for up to 26 years. All had telomere length measured in DNA from leukocytes, and 2052 of these were genotyped for the three single nucleotide polymorphisms rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1); all three genotypes are associated with telomere length and combined into an allele count from 0 to 6. For each telomere-lengthening allele, the hazard ratios (HRs) for mortality in the age-adjusted and multivariable-adjusted Cox analysis were 1.12 (95% confidence interval: 1.02-1.23) and 1.11 (1.01-1.23). However, for each standard deviation increase in measured telomere length, HR for mortality was 0.97 (0.88-1.08). In conclusion, in more than 2000 melanoma patients from hospital clinics and from the general population, genetically predicted long telomeres were associated with increased mortality, but measured leukocyte telomere length was not.

摘要

端粒长度的测量值和遗传预测值与黑色素瘤死亡率之间是否存在关联尚不清楚。我们检验了这样一个假设,即测量值和遗传预测值的端粒长度与黑色素瘤诊断后的死亡率有关。我们对 2101 名来自医院诊所和普通人群的黑色素瘤患者进行了随访,随访时间长达 26 年,以了解其死亡风险。所有患者的白细胞 DNA 端粒长度均有测量,其中 2052 名患者的三个单核苷酸多态性(rs7726159[TERT]、rs1317082[TERC]和 rs2487999[OBFC1])进行了基因分型;所有这三种基因型都与端粒长度有关,并结合成一个从 0 到 6 的等位基因计数。对于每个延长端粒的等位基因,在年龄调整和多变量调整的 Cox 分析中,死亡率的危险比(HR)分别为 1.12(95%置信区间:1.02-1.23)和 1.11(1.01-1.23)。然而,对于测量的端粒长度每增加一个标准差,死亡率的 HR 为 0.97(0.88-1.08)。总之,在来自医院诊所和普通人群的 2000 多名黑色素瘤患者中,遗传预测的长端粒与死亡率增加有关,但白细胞端粒长度的测量值则没有。

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Pigment Cell Melanoma Res. 2021 Sep;34(5):946-954. doi: 10.1111/pcmr.12971. Epub 2021 May 7.
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Low expression of SEMA4D as a potential predictive molecular marker of poor survival in patients with melanoma combined with liver cancer.
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Association Between Telomere Length and Skin Cancer and Aging: A Mendelian Randomization Analysis.端粒长度与皮肤癌及衰老之间的关联:一项孟德尔随机化分析。
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