Never smokers showed a higher frequency of alterations in EGFR, CTNNB1, SETD2, MET, and RB1. The occurrence of pathogenic or likely pathogenic germline variants was similar between smokers and never smokers (6.4% vs. 6.9%, respectively), nevertheless mutations in cancer predisposition genes (BRCA1, BRCA2, FANCG, FANCM, HMBS, MSH6, NF1, POLD1, TMEM127, and WRN) were observed only among never smokers. Here, EGFR is linked to cancer.