@article {LeePA4242, author = {So Yeon Lee and Seung Soo Yoo and Mi Jung Hong and Hye Won Seo and Yong Dae Lee and Keum Ju Choi and Jin Eun Choi and Hyo Gyoung Kang and Yangki Seok and Eung Bae Lee and Kyung Min Shin and Ji Yun Jeong and Won Kee Lee and Shin Yup Lee and Jaehee Lee and Seung Ick Cha and Chang Ho Kim and Young Tae Kim and Sanghoon Jheon and Jae Yong Park}, title = {A polymorphism, which exists intronic lesion of SLC5A10, affects DRG2 expression and survival outcome of early-stage non-small cell lung cancer}, volume = {46}, number = {suppl 59}, elocation-id = {PA4242}, year = {2015}, doi = {10.1183/13993003.congress-2015.PA4242}, publisher = {European Respiratory Society}, abstract = {RegulomeDB is a new tool that can predict regulatory functions of genetic variants. We investigated the association between putative functional variants selected using RegulomeDB and survival outcome of non-small cell lung cancer (NSCLC) via two independent cohort study. Total 244 variants with category 1a, which have the most confident evidence of variants affecting gene expression using RegulomeDB, were genotyped. Fourteen variants associated with overall survival (P \< 0.05) in discovery cohort were selected and examined using the validation cohort. One variant (rs2257609 C\>T) was validated. In a combined analysis, patients with rs2257609 CT or TT genotype exhibited a worse overall survival and disease free survival than those with rs2257609 CC genotype (hazard ratio [HR] = 1.87, 95\% confidence interval [CI] = 1.41 {\textendash} 2.48, P = 2.0 {\texttimes} 10-5 and HR = 1.44, 95\% CI = 1.16 {\textendash} 1.79, P = 0.001, respectively). DRG2 expression, which was predicted to be affected by rs2257609, was significantly higher in tumor tissues than non-malignant lung tissues (P = 0.001) and was different according to the rs2257609 genotype (Ptrend = 0.03). ). Luciferase assay also revealed higher promoter activity of DRG2 with rs2257609 T allele (P = 0.03). These results suggest that the rs2257609 C\>T may affect DRG2 expression and can be used as prognostic marker in early-stage NSCLC patients.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/46/suppl_59/PA4242}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }