在免疫抑制的固体器官移植接受者中鉴定皮细胞癌的遗传风险因素:一个病例对照研究
Raute Sunder-Plassmann1, Alexandra Geusau2, Georg Endler1
1Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Cancers
|July 14, 2023
概括
固体器官移植接受者由于免疫抑制而面临更高的角质细胞癌症风险. 基因分析确定了与多种状细胞癌症相关的关键基因,包括那些参与紫外线反应和瘤抑制的基因.
科学领域:
- 遗传学 遗传学 是一个
- 皮肤病学 皮肤病学
- 免疫学 免疫学 免疫学
背景情况:
- 固体器官移植接受者 (SOTRs) 由于长期免疫抑制,患上角质细胞癌 (KCs) 的风险较高.
- 了解导致SOTR中KC发展的遗传因素对于风险分层和预防至关重要.
研究的目的:
- 在实体器官移植接受者中确定与多个角质细胞癌症发生相关的遗传位置.
- 调查生殖线DNA变异在这种高风险人群中KC发育中的作用.
主要方法:
- 来自150名实体器官移植患者的生殖基因DNA的整体外基因组测序 (KCs和无瘤对照病例).
- 全基因组关联研究 (GWAS) 和针对罕见误解变异的小组测试 (Burden Zeggini测试).
- 对单核酸多态 (SNPs) 和与KC风险因素相关的基因路径的分析.
主要成果:
- 在EXOC3基因 (rs72698504) 中发现了一种SNP的全基因组显著关联.
- 在CYB561,WASHC1,PITRM1-AS1,MUC8,ABI3BP和THBS2-AS1中的几个变体 (p <10^-5) 与KC数量有关.
- 在MC1R,EPHA8,EPO,MYCT1,ADGRG3和MGME1的罕见误解变异和角质细胞癌症之间发现了强有力的关联 (p < 10^-6).
- 参与色素/紫外线保护,瘤抑制,免疫调节,细胞内交通和紫外线反应的基因被确定为遗传风险因素.
结论:
- 在实体器官移植受体中,遗传因素在多重角质细胞癌症的发展中起着重要作用.
- 参与细胞对紫外线辐射反应的基因与这一队列中KC风险增加有显著的关联.
- 这些发现突出了了解和管理免疫抑制个体的KC风险的潜在目标.
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