HOX transcript antisense intergenic RNA (HOTAIR) has been widely regarded as a functional lncRNA contributing to multiple cancers. However, few studies have examined the effect of single nucleotide polymorphisms (SNPs) in HOTAIR on the occurrence and development of hepatocellular carcinoma (HCC). In this study, three potentially functional HOTAIR SNPs (rs17105613, rs12427129, and rs3816153) were selected using bioinformatic tools. A case‐control study including 1262 cases and 1559 controls was conducted to explore the association of HOTAIR SNPs with the risk of HCC in a Southern Chinese population. We found that SNPs rs12427129 and rs3816153 were associated with the risk of HCC in dominant genetic models (CC: CT + TT, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.57–0.90 and GG: GT + TT, adjusted OR = 1.30, 95%CI = 1.08–1.57). Additionally, SNP–environment interactions for rs12427129, rs3816153, and HBsAg status were found to enhance the risk of HCC, with FDR‐P as an additive interaction equal to 0.0006 and 0.0144, respectively. In multifactor dimensionality reduction (MDR) analysis, the three‐factor model (HBsAg status, rs12427129 and rs3816153) yielded the highest test accuracy of 77.74% (permutation P < 0.001). Interestingly, the effect of rs12427129 and rs3816153 on the risk of HCC could be modified by HBsAg status, while the rs12427129 CT/TT genotype could antagonize the detrimental effect of rs3816153 GT/TT genotype on HCC. Our findings suggest that rs12427129 and rs3816153, including their SNP‐SNP and SNP‐environment interaction with HBsAg status, potentially play important roles on the susceptibility to HCC.

As a long non-coding RNA (lncRNA) and a transcriptional regulator, Metastasis associated lung adenocarcioma transcript-1 ( MALAT-1 ) has been reported to be associated with proliferation and metastasis of hepatocellular carcinoma (HCC). However, the effects of MALAT-1 single nucleotide polymorphisms (SNPs) on HCC remains poorly understood. This study, including 624 HCC cases and 618 controls, aimed to explore the potential associations between three common tagSNPs at MALAT-1 and HCC risk in a Southern Chinese population. No significant associations were observed between the three tagSNPs and HCC risk under any genetic models after adjusting for potential confounders. Additionally, there were no any significant associations in the stratified analysis, combined effect analysis, and multifactor dimensionality reduction (MDR) analysis. Unification analysis of mediation and interaction on HCC risk further showed that four decomposition of total effects ((controlled direct effect (CDE), the reference interaction effect (INTref), the mediated interaction effect (INTmed), or the pure indirect effect (PIE)) were also not significant. Neither was the association between the MALAT-1 SNPs and progression factors of HCC, including TNM staging, metastasis, and cancer embolus; Overall, this study suggested that tagSNPs rs11227209, rs619586, and rs3200401 at MALAT-1 were not significantly associated with HCC susceptibility. Nevertheless, large population-based studies are warranted to further explore the role of MALAT-1 SNPs in HCC incidence and development.

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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.