Interaction analysis between germline genetic variants and somatic mutations in head and neck cancer

To evaluate interactions between germline genetic variants and somatic mutations in head and neck cancer (HNC).The region enrichment analysis was performed to evaluate the enrichment of cancer driver genes (CDGs) in susceptibility regions. The pathway enrichment analysis was performed to identify common pathways of cancer driver genes and susceptibility genes. The association analysis was performed to evaluate the relationships between germline variants and somatic mutations. Stratified analysis was performed based on HPV status.A total of 18 risk SNPs, 149 cancer susceptibility genes (CSGs), and 211 CDGs were included. Enrichment analysis revealed that CDGs were significantly enriched in susceptibility regions (P = 0.048) and CSGs were significantly enriched in CDGs (P = 0.006). The CSGs and CDGs were commonly enriched in seven pathways. The rs1229984 was associated with truncation mutation within five pathways (P = 0.0026). The rs1453414 was associated with somatic mutations in RBM15 (P = 0.0012). The rs310518 was significantly associated with signature 15, and rs259919 was significantly associated with signature 6. The HPV status significantly influenced the association between risk SNPs and somatic mutations, copy number values, and mutation signatures.These results provide novel insights for germline-somatic interactions in HNC, which will enhance the understanding of the molecular mechanisms of germline variants with somatic mutations in HNC.