Association of genetic variants in lncRNA H19 with risk of colorectal cancer in a Chinese population

Abstract

Objective: The long non-coding RNA (lncRNA) gene, H19, has been involving in multiple biological functions, which also plays a vital role in colorectal cancer carcinogenesis. However, the association between genetic variants in H19 and colorectal cancer susceptibility has not been reported. In this study, we aim to explore whether H19 polymorphisms are related to the susceptibility of colorectal cancer.

Methods: We conducted a case-control study to evaluate the association between four selected single nucleotide polymorphisms (SNPs) (rs2839698, rs3024270, rs217727, and rs2735971) in H19 and the risk of colorectal cancer in a Chinese population.

Results: We found that individuals with rs2839698 A allele had a significantly increased risk of colorectal cancer, compared to those carrying G allele [odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.05-1.36 in additive model]. Further stratified analyses revealed that colon tumor site, well differentiated grade and Duke's stage of C/D were significantly associated with colorectal cancer risk (P < 0.05). Additionally, bioinformatic analysis showed that rs2839698 may change the crucial folding structures and alter the target microRNAs of H19.

Conclusions: Our results provided the evidence that rs2839698 in H19 was associated with elevated risk of colorectal cancer, which may be a potential biomarker for predicting colorectal cancer susceptibility.

Keywords: H19; colorectal cancer; genetic variation; long noncoding RNA; susceptibility.

Figure 1. Selected tagSNPs and relative position in H19

E1, E2, E3, E4, E5 and DMR indicates exon 1, exon 2, exon 3, exon 4, exon 5, and differentially methylated regions, respectively, whereas the line indicates the introns.

Figure 2. Bioinformatics prediction of rs2839698 on H19 folding structure

The folding structure alterations were demonstrated by RNAfold (A) and SNPfold (B), respectively. Arrow (A) indicates the change in structure caused by rs2839698. Arrow a indicates the position of rs2839698. Arrow G indicates the sequences of G allele, whereas arrow A indicates the A allele.