Four Novel Polymorphisms In Long Non-coding RNA HOTTIP Are Associated With The Risk And Prognosis Of Colorectal Cancer

Objective: The role of long non-coding RNA(lncRNA)HOTTIP as an oncogene in varieties of human cancer including colorectal cancer(CRC)has been clarified by extensive researches.The expression and function of lnc RNAs could be affected by single nucleotide polymorphisms(SNPs),which are associated with cancer susceptibility and prognosis.However,no investigation has focused on the association between HOTTIP SNPs and CRC.The present study aims to explore the relationship of polymorphisms in the lnc RNA HOTTIP gene with CRC risk and prognosis.Method: A total of 1848 subjects were enrolled in our study,including 884 CRC cases and 964 controls.Genotyping for five HOTTIP tag SNPs(rs3807598,rs17501292,rs2067087,rs17427960 and rs78248039)was performed applying the KASP method.Results: The results showed three SNPs(rs3807598,rs2067087 and rs17427960)were associated with enhanced CRC risk both in overall and stratified analysis.One polymorphism,rs17501292,could improve the overall survival(OS)of CRC patients in the subgroup with tumor of ulcerative/invasive type.Conclusion: These findings suggested HOTTIP SNPs might have potential to be predictive biomarkers for CRC risk and prognosis.Our study would provide clues for further exploration in novel lnc RNA-based genetic biomarkers for prediction of CRC susceptibility as well as clinical outcome.