Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

中文翻译：

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肺癌中MHC区域的精细定位突出显示了按种族划分的独立易感基因座。

肺癌在主要组织相容性复合体（MHC）中已鉴定出几种遗传关联。尽管这些关联的基础仍然难以捉摸。在这里，我们使用Illumina Illumina OncoArray或Illumina 660W SNP微阵列分析了26,044名肺癌患者和20,836名对照在整个MHC中的致密基因型之间的MHC遗传变异。我们估算经典HLA基因的序列变异，与主要组织学相关的MHC肺癌风险的精细图谱，并比较不同种族之间的结果。在欧洲人中发现了HLA基因内的独立和新颖关联，包括HLA-B * 0801肽结合槽中的氨基酸和独立的HLA-DQB1 * 06位点组。在亚洲人中，协会由两个独立的HLA等位基因组驱动，这两个组均会增加HLA-DQB1 * 0401和HLA-DRB1 * 0701的风险；后者更好地由氨基酸Ala-104代表。这些结果暗示了几种HLA-肿瘤肽相互作用是调节肺癌易感性的主要MHC因子。