Regulatory variants in cancer-related pathway genes predict survival of patients with surgically resected non-small cell lung cancer.
BACKGROUND
We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB.


METHOD
A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n=354), and a replication study was performed in an independent set (n=772). The association of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed.


RESULTS
In the discovery set, 76 SNPs were significantly associated with OS or DFS. Among the 76 SNPs, the association was consistently observed for 5 SNPs (ERCC1 rs2298881C>A, BRCA2 rs3092989G>A, NELFE rs440454C>T, PPP2R4 rs2541164G>A, and LTBP4 rs3786527G>A) in the validation set. In combined analysis, ERCC1 rs2298881C>A, BRCA2 rs3092989, NELFE rs440454C>T, and PPP2R4 rs2541164G>A were significantly associated with OS and DFS (adjusted HR ·aHR· for OS=1.46, 0.62, 078, and 0.76, respectively; P=0.003, 0.002, 0.007, and 0.003 respectively; and aHR for DFS=1.27, 0.69, 0.86, and 0.82, respectively; P=0.02, 0.002, 0.03, and 0.008, respectively). The LTBP4 rs3786527G>A was significantly associated with better OS (aHR=0.75; P=0.003).


CONCLUSION
Our results suggest that five SNPs in the cancer-related pathway genes may be useful for the prediction of the prognosis in patients with surgically resected NSCLC.
['Shin|Kyung Min|KM|', 'Hong|Mi Jeong|MJ|', 'Lee|Shin Yup|SY|', 'Jin|Cheng Cheng|CC|', 'Baek|Sun Ah|SA|', 'Lee|Jang Hyuck|JH|', 'Choi|Jin Eun|JE|', 'Kang|Hyo-Gyoung|HG|', 'Lee|Won Kee|WK|', 'Seok|Yangki|Y|', 'Lee|Eung Bae|EB|', 'Jeong|Ji Yun|JY|', 'Yoo|Seung Soo|SS|', 'Lee|Jaehee|J|', 'Cha|Seung Ick|SI|', 'Kim|Chang Ho|CH|', 'Kim|Young Chul|YC|', 'Oh|In Jae|IJ|', 'Na|Kook Joo|KJ|', 'Cho|Sukki|S|', 'Jheon|Sanghoon|S|', 'Park|Jae Yong|JY|']
D002289:Carcinoma, Non-Small-Cell Lung D019295:Computational Biology D005260:Female D053263:Gene Regulatory Networks D005838:Genotype D006801:Humans D008175:Lung Neoplasms D008297:Male D020641:Polymorphism, Single Nucleotide D011379:Prognosis D016019:Survival Analysis D016896:Treatment Outcome
Survival Lung cancer Polymorphism RegulomeDB