Abstract 2473: Association of functional genetic variants of long noncoding RNA HOTAIR with oral cancer susceptibility

<jats:title>Abstract</jats:title>
<jats:p>Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). Polymorphisms in the HOX transcript antisense intergenic RNA (HOTAIR) have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HOTAIR gene, rs920778, rs1899663, rs4759314, and rs12427129 were tested in 1200 normal controls and 907 OSCC patients. We detected a significant association of rs1899663 with the risk of OSCC (AOR, 2.227; 95% CI, 1.197-4.146; p=0.012) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. In the further analyses where habitual exposure to each of three environmental factors was individually excluded, we found that, in addition to rs1899663, non-betel nut users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: OR, 1.472; 95% CI, 1.069-2.029; p=0.018; TC+CC: OR, 1.448; 95% CI, 1.060-1.977; p=0.020). This genetic association was not seen while comparing subjects who do not smoke or consume alcohol between the case and control cohort. Moreover, as exploring the relationship between HOTAIR gene polymorphisms and clinical status of only OSCC patients who were non-betel nut chewers, besides the association with the advanced clinical stage, rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027-3.484; p=0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785-9.602; p=0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel nut chewing on the development and progression of oral cancer.</jats:p>
<jats:p>Citation Format: Shun-Fa Yang, Shih-Chi Su, Chiao-Wen Lin. Association of functional genetic variants of long noncoding RNA HOTAIR with oral cancer susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2473.</jats:p>