Associations of the Expression Levels and Risk Variants of <i>CDKN2B‐AS1</i> Long Noncoding <scp>RNA</scp> With the Susceptibility and Progression of Prostate Cancer

Genetic variants of deregulated long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, cancer progression and cancer recurrence. Single-nucleotide polymorphisms (SNPs) of the lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) have been associated with the risk and progression of various cancers; however, their role in prostate cancer (PCa) remains underexplored. In this case-control study, we investigated the associations of CDKN2B-AS1 expression levels and variants with PCa risk and progression. For this, five SNPs of CDKN2B-AS1-rs564398, rs1333048, rs1537373, rs2151280 and rs8181047-were genotyped using a TaqMan allelic discrimination assay; data were collected from 695 patients with PCa and 695 healthy controls. Our findings revealed that, under a dominant model, patients with PCa carrying at least one minor C allele of rs1333048 exhibited an increased risk of developing tumours with high Gleason grades; this risk was particularly high in patients without biochemical recurrence. Data from the Genotype-Tissue Expression database indicated upregulated CDKN2B-AS1 expression in the prostates of individuals carrying the polymorphic C allele of rs1333048. Genotype screening of rs1333048 in PCa cell lines showed that cells with at least one minor C allele had higher CDKN2B-AS1 levels than those with the AA genotype. Furthermore, data from The Cancer Genome Atlas indicated that higher CDKN2B-AS1 levels in PCa tissues were correlated with larger tumour sizes (T3 + T4), more lymph node metastasis (N1), higher Gleason scores and shorter progression-free survival. In conclusion, the polymorphic variants of CDKN2B-AS1 at rs1333048 may modulate CDKN2B-AS1 expression, thus accelerating PCa progression.