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The association of polymorphisms in lncRNA-H19 with hepatocellular cancer risk and prognosis.

ABSTRACT: Hepatocellular cancer (HCC) is one of the major causes of cancer-related mortality. Genetic polymorphisms may affect the susceptibility and clinical outcomes of cancers. We aim to manifest the association of single nucleotide polymorphisms (SNPs) of lncRNA-H19 gene with the risk and prognosis of HCC. A total of 944 samples composed of 472 HCC patients and 472 matched controls were included in the risk analysis and amongst them 350 HCC samples were investigated in the prognosis analysis. KASP method was conducted for the SNP genotyping. The TT + CT genotype of rs2839698 was found to be associated with a 1.32-fold increased HCC risk (P=0.037, 95% confidence interval (CI) = 1.02-1.70). In the stratified analysis, rs2839698 (odds ratio (OR) = 1.57, P=0.007, 95% CI = 1.13-2.18) and rs3024270 (OR = 1.71, P=0.019, 95% CI = 1.09-2.68) were found to show more obvious increased HCC risk in the age ?60 subgroup. And we found that rs2839698 showed an increased HCC risk in the ever smoking subgroup. But in the male subgroup of rs2735971, it showed a decreased HCC risk. Furthermore, haplotype analysis showed that rs2735971-rs2839698-rs3024270 G-T-C significantly increased the risk of HCC (OR = 1.23, 95% CI = 1.01-1.51, P=0.043). Multilogistic analysis revealed no significant results of the interaction effects of the SNPs and environment factors. And in our study, rs2839698 showed a significant poor prognosis in the ever smoking subgroup (hazard rate (HR) = 5.19, 95% CI = 1.12-24.07, P=0.035). lncRNA-H19 rs2839698 SNP has the potential to be predictors for HCC risk and prognosis.

SUBMITTER: Yang ML

PROVIDER: S-EPMC6123070 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Project description:Background:The long non-coding RNA H19 plays critical roles in cancer occurrence, development, and progression. The present study is for the first time to evaluate the association of genetic variations in the H19 promoter region with advanced colorectal cancer (CRC) susceptibility, environmental factors, and clinical outcomes. Methods:16 single-nucleotide polymorphisms (SNPs) were identified in the H19 gene promoter by DNA sequencing, and 3 SNPs among which including rs4930101, rs11042170, and rs2735970 further expanded samples with 572 advanced CRC patients and 555 healthy controls. Results:We found that harboring SNP [rs4930101 (P?=?0.009), rs2735970 (P?=?0.003), and rs11042170 (P?=?0.003)] or carrying more than one combined risk genotypes significantly increased the risk for CRC [P?<?0.0001, adjusted OR (95% CI) 6.48 (2.97-14.15)]. In the correlation analysis with environmental factors, rs2735970 and gender, combined risk genotypes (>?1 vs.???1) and family history of cancer demonstrated significant interactions. Furthermore, a remarkably worse clinical outcome was found in combined risk genotypes (>?1 vs.???1), especially in CRC patients with body weight???61 kg, smoking, and first-degree family history of cancer (Log-rank test: P?=?0.006, P?=?0.018, and P?=?0.013, respectively). More importantly, the multivariate Cox regression analyses further verified that combined risk genotypes?>?1 showed a prognostic risk factor for CRC patients with body weight???61 kg (P?=?0.002), smoking (P?=?0.008), and family history of cancer (P?=?0.006). In addition, MDR analysis consistently revealed that the combination of selected SNPs and nine known risk factors showed a better prediction prognosis and represented the best model to predict advanced CRC prognosis. Conclusion:3 SNPs of rs4930101, rs11042170, and rs27359703 among 16 identified SNPs of H19 gene remarkably increased CRC risk. Furthermore, the combined risk genotypes had a significant impact on environmental factors and clinical outcomes in the advanced CRC patients with body weight???61 kg, ever-smoking, and first-degree family history of cancer. These data suggest that H19 promoter SNPs, especially these combined SNPs might be more potentially functional biomarkers in the prediction of advanced CRC risk and prognosis.

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The association of polymorphisms in lncRNA-H19 with hepatocellular cancer risk and prognosis.

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