JAMA netw open:人类白细胞抗原和其他位点单核苷酸变异与儿童霍奇金淋巴瘤的关系

2022-08-10 liangying MedSci原创

在儿童期和成人期发病的HL之间存在一种普遍且独特的遗传病因相关机制。

霍奇金淋巴瘤(HL)起源于B淋巴细胞,最常见于20-34岁人群(30.7%),儿童和年轻人(<20岁)占HL患者的12.2%。尽管HL在5岁以下儿童中的发病率较低,但它是15至19岁青少年和年轻成年人中最常见的癌症,5年生存率超过95%。
虽然儿童HL的5年生存率较高,但在儿童期发病的HL治愈后,化疗和放疗的晚期效应很常见,可能会导致衰老加速和过高的晚期死亡率,关于儿童霍奇金淋巴瘤(HL)遗传易感性的研究是有限的。本研究的目的是确定儿童期和成人期HL发病相关的遗传变异。
这项基因关联研究由3个队列进行:2007年启动的St Jude终生队列研究(SJLIFE)持续随访,以及1990年代启动的儿童癌症幸存者研究(CCSS)的原始和扩展队列持续随访。通过荟萃分析将这些全基因组关联研究(GWAS)的结果结合起来。数据分析时间为2021年6月至2022年6月。
儿童期HL是重点结果。对CCSS原始队列进行单核苷酸变异(SNV,以前称为单核苷酸多态性)阵列基因分型和插补,并对SJLIFE和CCSS扩展队列进行全基因组测序。
共有1286例HL(平均诊断[SD]年龄,14.6[3.9]岁)、6193例非HL儿童癌症病例和369例非癌症对照纳入分析,均为欧洲血统。使用逐步条件logistic回归,在人类白细胞抗原(HLA)基因座中确定的3个独立SNV的优势比(OR)分别为RS2838311:1.80、rs3129198:1.53和rs3129890:1.51。进一步的HLA插补揭示了9个等位基因和55个氨基酸的变化,可能导致HL易感性。
HLA等位基因与霍奇金淋巴瘤易感性的关系
 
此外,还发现了5个非HLA位点:(1)rs1432297;(2) rs2757647;(3) rs13279159;(4) rs3824662;和(5)rs117953624,一种新的不常见SNV,映射到PDGFD。先前报道的18个全基因组显著非HLA SNV中有12个(67%)被复制,结果具有统计学意义。
总之,这项遗传相关性研究发现,在儿童期和成人期发病的HL之间存在一种普遍且独特的遗传病因相关机制
 
参考文献:
Chen C, Song N, Dong Q, et al. Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma. JAMA Netw Open. 2022;5(8):e2225647. doi:10.1001/jamanetworkopen.2022.25647

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    2023-05-10 canlab
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    2023-06-14 feather89
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    2023-01-06 xsm918
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    2022-08-09 肿瘤克星

    JAMA上文章都是顶级的,谢谢梅斯及时上新

    0

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