Compared with 15 MR studies on circulating proteins and LC risk identified through our systematic review (S34 and S35 Tables), 10 protein-LC associations were further validated (LC: IL19, MICB_MICA, TSG101, and CTF1; LUSC: PDE5A and TIE1; LUAD: MCF2L and RPN1; and SCLC: GLRX2 and TREM1), while the remaining 15 causal associations represent novel findings (LC: RPL14, STX4, UBE2L6, S100A4, BTN3A1, CEP43, MPI, and TNFAIP8L2; LUSC: ADM2, USP28, AGER, and BRD2; LUAD: CTBS and ELOA; and SCLC: DAG1). Here, TIPE2 is linked to laryngotracheoesophageal cleft.