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Yuan, H.M.* ; Liu, H.* ; Liu, Z.* ; Owzar, K.* ; Han, Y.* ; Su, L.* ; Wei, Y.* ; Hung, R.J.* ; McLaughlin, J.* ; Brhane, Y.* ; Brennan, P.* ; Bickeboeller, H.* ; Rosenberger, A.* ; Houlston, R.S.* ; Caporaso, N.* ; Landi, M.T.* ; Heinrich, J. ; Risch, A.* ; Christiani, D.C.* ; Gümüå, Z.H.* ; Klein, R.J.* ; Amos, C.I.* ; Wei, Q.*

A novel genetic variant in long non-coding RNA gene NEXN-AS1 is associated with risk of lung cancer.

Sci. Rep. 6:34234 (2016)

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Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10-7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11-1.24; P = 8.31 × 10-9). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

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