In a validation study on 63 ever-smoking LC patients and 90 matched controls, a risk score based on four circulating protein biomarkers (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], precursor form of surfactant protein B [pro-SFTB]) considerably improved the USPSTF eligibility criteria (area under the curve [AUC] 0.83 [95% confidence interval (CI), 0.76–0.90] vs. AUC 0.73 [95% CI, 0.64–0.82]; p = 0.003) and 1-year LC prediction [34]. This evidence concerns the gene MUC16 and laryngotracheoesophageal cleft.