HOTTIP polymorphism may affect gastric cancer susceptibility by altering HOTTIP expression

Background: Non-coding RNA polymorphisms can affect disease risk and prognosis by influencing gene expression. Here, we first investigated the association between single nucleotide polymorphisms (SNPs) of long non-coding RNA (lncRNA) HOTTIP and gastric cancer risk/prognosis. Methods: A total of five HOTTIP SNPs among 627 gastric cancer cases and 935 controls were tested by Kompetitive Allele Specific PCR (KASP) assay. The functional SNPs underwent eQTL analysis and the expression of HOTTIP was assessed by quantitative RT-PCR. Results: The rs2067087 and rs3807598 SNPs of HOTTIP increased susceptibility to gastric cancer (rs2067087: dominant model, P=0.008, odds ratio (OR) = 1.35; rs3807598: recessive model, P=0.037, OR = 1.29). Both HOTTIP rs2067087 and rs3807598 could affect the expression of mature lncRNA (P=0.003 and P=0.032, respectively). Conclusion: The rs2067087 and rs3807598 SNPs of HOTTIP are associated with gastric cancer risk, possibly by affecting the expression of mature HOTTIP.