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.
Highlights
Hepatocellular cancer (HCC) is the major liver malignancy that attributes toward the second foremost cause of cancer-related mortality worldwide [1]
In the subgroup stratified by age, rs2839698 showed an obvious HCC risk tendency in CT genotype of age ≤60 subgroup (OR = 1.57, P=0.007) and the similar situation was showed in rs3024270 CC genotype of age ≤60 subgroup (OR = 1.71, P=0.019)
H19 gene, with the length of 2.3 kb and located in 11p15.5, containing five exons and three introns [22], which has been well accepted that lncRNA-H19 plays an important role in the development, migration, invasion, and metastasis of cancers [23]
Summary
Hepatocellular cancer (HCC) is the major liver malignancy that attributes toward the second foremost cause of cancer-related mortality worldwide [1]. There are many single nucleotide polymorphisms (SNPs) that have been reported to be related to HCC risk in some coding and non-coding genes and have manifested great significance for the selection of individuals who would benefit from the specific diagnostic and preventative measures [3]. Many studies have reported that H19 as an oncogene lncRNA in multiple cancers, such as, colorectal cancer [11], gastric c 2018 The Author(s).
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