# Disease‐Associated Risk Variants and Expression Levels of the lncRNA, CDKN2B‐AS1, Are Associated With the Progression of HCC

## TL;DR

This study explores how genetic variations in the lncRNA CDKN2B-AS1 affect the risk and progression of liver cancer in a Taiwanese population.

## Contribution

The study identifies specific SNPs in CDKN2B-AS1 linked to reduced HCC risk and progression in a population-specific context.

## Key findings

- The rs564398 C-allele is associated with a lower risk of liver cirrhosis in HCC patients.
- The rs1537373 GT+TT genotype is linked to reduced risk of large tumors and advanced stages in male HCC patients.
- CDKN2B-AS1 expression is higher in HCC tissues and correlates with poor prognostic factors.

## Abstract

The most susceptible loci of hepatocellular carcinoma (HCC) identified by genome‐wide association studies are located in non‐coding regions. The antisense non‐coding RNA at the INK4 locus (ANRIL), also known as cyclin‐dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B‐AS1), is a long non‐coding (lnc)RNA situated within and antisense to genes encoding CDKN2A/B on chromosome 9p21.3. Single‐nucleotide polymorphisms (SNPs) within CDKN2B‐AS1 are associated with several cancer types, but their impacts on HCC remain unclear. In this study, we investigated the effects of CDKN2B‐AS1 SNPs on both the susceptibility to HCC and its clinicopathological development. Five CDKN2B‐AS1 SNP loci—rs564398 (T/C), rs1333048 (A/C), rs1537373 (G/T), rs2151280 (A/G) and rs8181047 (G/A)—were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 810 HCC patients and 1190 healthy controls. Under the dominant model, HCC patients with at least one minor C‐allele of rs564398 showed a lower risk of liver cirrhosis (odds ratio (OR) = 0.677). Additionally, HCC patients with the GT + TT genotype of rs1537373 had a reduced risk of developing large tumours (T3 + T4) and advanced clinical stages (III/IV), particularly in the male population (OR = 0.644 and 0.679). Furthermore, data from The Cancer Genome Atlas revealed that CDKN2B‐AS1 expression levels were elevated in HCC tissues compared to normal tissues and were correlated with advanced T stages, high histological grades and poor prognoses. Our findings suggest that CDKN2B‐AS1 levels and its polymorphic variants at rs564398 and rs1537373 may influence the clinicopathological development and progression of HCC in a Taiwanese population.