Notably, one healthy individuals in a familial family (marked with arrows in Fig. 2g, Fig. 3 and Supplementary Table S6) exhibited features identical to those of patients with familial LC, including a large and interconnected main graph of the germline SNP-containing genes (Fig. 2g), “Pathways in Cancer” and the PI3K/AKT pathway as the top two KEGG pathways (Supplementary Table S6), and 24 and 20 SNP-containing genes in the two pathways, respectively (Fig. 3). This evidence concerns the gene PIK3CA and laryngotracheoesophageal cleft.