The association of lncRNA SNPs and SNPs‐environment interactions based on GWAS with HBV‐related HCC risk and progression

BACKGROUND: Long non‐coding RNA (lncRNA) plays an essential role in hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) occurrence and development. Single nucleotide polymorphism (SNP) may affect HBV‐related HCC susceptibility by altering the function of lncRNA. However, the relationship between lncRNA SNPs and HBV‐related HCC occurrence and development is still unclear. METHODS: In the present study, based on HBV‐related HCC genome‐wide association studies, eight potentially functional SNPs from two lncRNAs were predicted using a set of bioinformatics strategies. In 643 HBV‐related HCC patients, 549 CHB carriers, and 553 HBV natural clearance subjects from Southern Chinese, we evaluated associations between SNPs and HBV‐related HCC occurrence or development with odds ratio (OR) and 95% confidence interval (CI) under credible genetic models. RESULTS: In HBV‐related HCC patients, rs9908998 was found to significantly increase the risk of lymphatic metastasis under recessive model (Adjusted OR = 1.95, 95% CI = 1.20–3.17). Lnc‐RP11‐150O12.3 rs2275959, rs1008547, and rs11776545 with cancer family history may show significant multiplicative and additive interactions on HBV‐related HCC susceptibility (all p (Adjusted) < .05). The associations of rs2275959, rs1008547, and rs11776545 with distant metastasis of HBV‐related HCC patients were observed in additive model (Adjusted OR = 1.45, 95% CI = 1.06–1.97 for rs2275959; Adjusted OR = 1.45, 95% CI = 1.06–1.98 for rs1008547; Adjusted OR = 1.40, 95% CI = 1.03–1.91 for rs11776545). CONCLUSION: Taken together, lnc‐ACACA‐1 rs9908998, lnc‐RP11‐150O12.3 rs2275959, rs1008547, and rs11776545 might be predictors for HBV‐related HCC risk or prognosis.