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 pAdjusted < .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.