Interactive effects of CDKN2B-AS1 gene polymorphism and habitual risk factors on oral cancer

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant disease associated with a high mortality rate and heterogeneous disease aetiology. Cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), is a long noncoding RNA that has been shown to act as a scaffold, sponge, or signal hub to promote carcinogenesis. Here, we attempted to assess the effect of CDKN2B-AS1 single-nucleotide polymorphisms (SNPs) on the susceptibility to OSCC. Five CDKN2B-AS1 SNPs, including rs564398, rs1333048, rs1537373, rs2151280 and rs8181047, were analysed in 1060 OSCC cases and 1183 cancer-free controls. No significant association of these five SNPs with the risk of developing OSCC was detected between the case and control group. However, while examining the clinical characteristics, patients bearing at least one minor allele of rs1333048 (CA and CC) were more inclined to develop late-stage (stage III/IV, adjusted OR, 1.480; 95% CI, 1.129-1.940; p = 0.005) and large-size (greater than 2 cm in the greatest dimension, adjusted OR, 1.347; 95% CI, 1.028-1.765; p = 0.031) tumours, as compared with those homologous for the major allele (AA). Further stratification analyses demonstrated that this genetic correlation with the advanced stage of disease was observed only in habitual betel quid chewers (adjusted OR, 1.480; 95% CI, 1.076-2.035; p = 0.016) or cigarette smokers (adjusted OR, 1.531; 95% CI, 1.136-2.063; p = 0.005) but not in patients who were not exposed to these major habitual risks. These data reveal an interactive effect of CDKN2B-AS1 rs1333048 with habitual exposure to behavioural risks on the progression of oral cancer.

Keywords: cyclin dependent kinase inhibitor 2B antisense RNA 1; long noncoding RNA; oral squamous cell carcinoma; single-nucleotide polymorphism.

FIGURE 1

CDKN2B‐AS1 expression levels are increased and associated with clinicopathological parameters in head and neck squamous cell carcinoma (HNSCC). (A) Comparison of CDKN2B‐AS1 expression between tumour and normal tissues. (B–D) Correlations of CDKN2B‐AS1 expression with the clinical staging (B), lymphatic spread (C) and tumour size (D) of HNSCC from The Cancer Genome Atlas (TCGA) database. The total number of samples is given in brackets. p‐Values are calculated with student's t‐test.