This study investigated gene mutations in a Han Chinese family of lung cancer using the whole genome exome sequencing and subsequent Sanger sequencing validation and then confirmed alteration of prominin 1(PROM1) and cyclic AMP-response element binding protein-regulated transcription co-activator2 (CRTC2) in blood samples of 343 sporadic lung cancer patients vs. 280 healthy controls as well as in 200 pairs of lung cancer and the corresponding normal tissues using PCR-restriction fragment length polymorphism and directed DNA sequencing of PCR products. Here, CRTC2 is linked to lung cancer.