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Association of expression quantitative trait loci for long noncoding RNAs with lung cancer risk in Asians.

Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected the lncRNAs that differently expressed based on the Cancer Genome Atlas (TCGA) project (75 normal and 708 tumor tissues) and identified eQTLs for selected lncRNAs based on data of 278 normal lung tissues from the the genotype-tissue expression database. Then we selected lncR-eQTLs that associated with lung cancer based on two lung cancer GWAS datasets (7127 cases and 6818 controls). Promising lncR-eQTLs were further replicated in an additional population (1056 cases and 1053 controls). Functional annotations of the identified lncR-eQTLs and related lncRNAs were finally performed by using multiple public databases. Our eQTL analysis finally detected three lncRNA-eQTLs, rs793544 in 3q13.12 (odds ratio [OR] = 1.15; confidence interval [CI]:1.09-1.22; P = 2.30 × 10-6 ), rs7234707 in 18p11.31 (OR = 1.1; CI:1.05-1.15; P = 9.01 × 10-5 ) and rs1600249 in 8p23.1 (OR = 1.1; CI:1.05-1.16; P = 1.27 × 10-4 ), that were consistently associated with the risk of lung cancer. These findings indicate that lncR-eQTLs may serve as novel susceptibility markers for lung cancer.

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