Nat Commun:两个大型队列鉴定出相同的癌症遗传风险

2020-09-05 haibei MedSci原创

当前,癌症的全球负担是巨大的,每年估计有1810万人被诊断出癌症,约960万人死于癌症。因此,对癌症的预防,筛查和治疗是不可缺少的,但这需要我们对致癌的基础有一个更全面的了解。

当前,癌症的全球负担是巨大的,每年估计有1810万人被诊断出癌症,约960万人死于癌症。因此,对癌症的预防筛查和治疗是不可缺少的,但这需要我们对致癌的基础有一个更全面的了解。

虽然在双胞胎,家族,和不相关的人群中的研究已经证明了大量的具有遗传性和家族集群特征的癌症,但是我们对于不同癌症中遗传变异的独特和共通之处并不清楚。

个体癌症的全基因组关联研究(GWAS)已经确定了与多种癌症类型相关的位点,包括1q32(MDM4); 2q33(CASP8-ALS2CR12);3q28(TP63); 4q24(TET2); 5p15(TERT-CLPTM1L); 6p21(HLA复合物); 7p1517; 8q2412; 11q1318; 17q12(HNF1B); 和19q13(MERIT40)。此外,最近的研究也测试以前与一种癌症相关的单核苷酸多态性(SNPs)与其他癌症类型的关联。破译不同癌症的共同遗传基础有可能阐明致癌机制,并为广泛适用的风险评估工作提供信息。

最近,研究人员在Nature Communications杂志发文,报导了其在两个大型的、基于人群的队列中进行了全基因组关联研究(GWAS)和18种癌症类型的遗传性和多态性综合评估。两个队列包括英国生物库(408,786名欧洲血统个体;48,961个癌症病例)和Kaiser Permanente成人健康和老龄化遗传流行病学研究队列(66,526名欧洲血统个体;16,001个癌症病例)。

在对UKB和GERA结果进行荟萃分析后,研究人员发现21个以前未报道的变异体与癌症之间的全基因组显著关联,P<5×10-8。这包括20个独特的变异,其中1个变异与两种癌症相关(rs78378222)。这21个关联中的9个位于其感兴趣的癌症的已知易感区域,但独立于先前报道的变异(r2<0.1)。其余12个关联位于欧洲血统的个体中与感兴趣的癌症没有关联的区域。

在这21个关联中,有14个关联显示出多向性,即变异所在区域在先前的评估中与至少一种其他癌症类型相关。

当按诊断时的年龄、监测、流行病学和最终结果计划(SEER)等级或SEER阶段进行分层时,这21个关联的效应估计没有实质性变化(异质性P>0.05/[分层和变异的数量])。

对多态性的调查确定了12个表现出阳性或阴性遗传相关性的癌症对;25个多态性位点;以及100个独立的多态性变异,其中许多是调节元素和/或影响跨组织基因表达。

因此,该研究结果证明了广泛的多态性,并为跨癌易感性的复杂遗传结构提供了进一步的认识。

 

原始出处:

Sara R. Rashkin et al. Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts. Nature Communications (2020). 

 

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