Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, whose diversified occurrence worldwide indicates a connection between genetic variations among individuals and the predisposition to such neoplasms. Mounting evidence has demonstrated that long non-coding RNA (lncRNA) H19 can have both promotive and inhibitory effects on cancer development, revealing a dual role in tumorigenesis. In this study, the link of H19 gene polymorphisms to hepatocarcinogenesis was assessed between 359 HCC patients and 1190 cancer-free subjects. We found that heterozygotes for the minor allele of H19 rs2839698 (T) and rs3741219 (G) were more inclined to develop HCC (OR, 1.291; 95% CI, 1.003–1.661; p = 0.047, and OR, 1.361; 95% CI, 1.054–1.758; p = 0.018, respectively), whereas homozygotes for the polymorphic allele of rs2107425 (TT) were correlated with a decreased risk of HCC (OR, 0.606; 95% CI, 0.410–0.895; p = 0.012). Moreover, patients who bear at least one variant allele (heterozygote or homozygote) of rs3024270 were less prone to develop late-stage tumors (for stage III/IV; OR, 0.566; 95% CI, 0.342–0.937; p = 0.027). In addition, carriers of a particular haplotype of three H19 SNPs tested were more susceptible to HCC. In conclusion, our results indicate an association between H19 gene polymorphisms and the incidence and progression of liver cancer.
Highlights
Hepatocellular carcinoma (HCC) is currently the sixth most common type of malignancy with a high death rate and an increasing incidence globally [1]
These findings suggest that an individual’s gene polymorphisms influence oxidative stress, DNA repair, iron metabolism, cell signaling, inflammatory and immune responses, which contribute to the predisposition to hepatocarcinogenesis and partly address the global heterogeneous incidence of HCC
Since various risk factors, such as age, gender, alcohol consumption, and tobacco use have been demonstrated to contribute to the etiology and pathogenesis of liver cancer [37,38], we first compared the demographic information of 359 HCC patients with that from 1190 normal controls (Table 1)
Summary
Hepatocellular carcinoma (HCC) is currently the sixth most common type of malignancy with a high death rate and an increasing incidence globally [1]. Recent studies have revealed that single-nucleotide polymorphisms (SNPs) are associated with the formation of hepatic neoplasm independently or together with the recognized risk factors in particular ethnic populations [6,7,8]. These findings suggest that an individual’s gene polymorphisms influence oxidative stress, DNA repair, iron metabolism, cell signaling, inflammatory and immune responses, which contribute to the predisposition to hepatocarcinogenesis and partly address the global heterogeneous incidence of HCC. Extensive transcriptomic investigations have connected the delicate orchestration of lncRNA expression to cancer initiation and poor outcome in various tumors, and surveys of cancer genomes have uncovered a catalogue of functional variants within the lncRNA genes [13,14], highlighting a strong link between tumorigenesis and the modulation of lncRNAs
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