Lancet Oncol:发现结外自然杀伤T细胞淋巴瘤的新风险位点

2019-12-26 不详 MedSci原创

结外自然杀伤T细胞淋巴瘤(NKTCL;鼻型)是一种恶性肿瘤,在亚洲和拉丁美洲人群中发病率特别高。EB病毒感染在NKTCL的发病机制中具有一定作用,HLA-DPB1变异是该病的危险因素。研究人员在中国汉族人群中开展一项对NKTCL的全基因组关联分析研究,以筛选新的NKTCL的危险变异。共招募了两个队列,筛查队列:700位NKTCL患者和7752位对照,重复队列:717位患者和12650位对照。200

结外自然杀伤T细胞淋巴瘤(NKTCL;鼻型)是一种恶性肿瘤,在亚洲和拉丁美洲人群中发病率特别高。EB病毒感染在NKTCL的发病机制中具有一定作用,HLA-DPB1变异是该病的危险因素。

研究人员在中国汉族人群中开展一项对NKTCL的全基因组关联分析研究,以筛选新的NKTCL的危险变异。共招募了两个队列,筛查队列:700位NKTCL患者和7752位对照,重复队列:717位患者和12650位对照。

2008年1月1日-2019年1月23日,收集遗传信息。通过对所有样本进行Meta分析,筛查出两个与NKTCL显著相关的新位点:2q12.1 上的IL18RAP(rs13015714,优势比[OR]1.39)和6p21.3上的HLA-DRB1(rs9271588,OR 1.53)。此外,进一步研究发现IL18RAP启动子上的rs1420106与rs13015714位点密切相关,rs1420106上的A等位基因具有上调IL18RAP表达的作用。NKTCL细胞(YT和SNK-6细胞)实验显示敲除IL18RAP可通过细胞周期阻滞抑制细胞增殖。核型相关性分析显示单倍体47F-67I与NKTCL风险降低有关,而47Y-67I与NKTCL风险升高相关。这两个基因所编码的蛋白都是HLA-DR异源二聚体的肽结合口袋7 (P7)的组成成分,提示这些变异可能解释了HLA-DRB1的相关性,与既往报道的HLA-DPB1变体无关。

本研究为NKTCL的发展提供了新的见解,通过IL18-IL18RAP轴和HLA-DRB1抗原提呈揭示了炎症和免疫调节的重要意义,有助于寻找潜在的治疗靶点。结合其他遗传因素和其他风险因素,本研究结果或可用于对NKTCL高危人群进行分层,从而进行针对性预防

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    2020-08-29 howi
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    2020-05-11 minlingfeng
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    2019-12-26 anti-cancer

    谢谢梅斯分享这么多精彩信息

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