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World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2017

Open Access 01-12-2017 | Research

rs1859168 A > C polymorphism regulates HOTTIP expression and reduces risk of pancreatic cancer in a Chinese population

Authors: Pinghai Hu, Ou Qiao, Jun Wang, Jiao Li, Hao Jin, Zhaolian Li, Yan Jin

Published in: World Journal of Surgical Oncology | Issue 1/2017

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Abstract

Background

Long non-coding RNAs (lncRNAs) are aberrantly expressed in many types of human cancer including pancreatic cancer (PC) and correlated with tumorigenesis and cancer prognosis, whereas knowledge about regulatory mechanism of lncRNA expression is few known. This study aimed to explore whether polymorphisms in lncRNAs genes are associated with PC susceptibility by affecting its expression.

Methods

We first genotyped three common single-nucleotide polymorphisms (SNPs) of lncRNA genes (HOTTIP rs1859168, HOTAIR rs4759314, and H19 rs217727) in 416 paired PC patients and controls, and then validated the results in another 505 paired PC patients and controls. The genotype-phenotype correlation was examined in 50 PC tissue samples with different genotypes as well as by luciferase reporter assay.

Results

In the discovery set, only the HOTTIP rs1859168 A > C showed to be significantly associated with a reduced PC risk (CC vs AA: odds ratio (OR) = 0.71, 95% confidence interval (95%CI) = 0.57–0.88, P = 0.002; recessive model: adjusted OR = 0.51, 95%CI = 0.38–0.68, P < 0.001; additive model: adjusted OR = 0.67, 95%CI = 0.51–0.82, P < 0.001). The results in validation set and pooled population also indicated that the C allele of HOTTIP rs1859168 could significantly decrease the risk of PC. In addition, the genotype-phenotype association analysis suggested that HOTTIP expression level was significantly lower in PC samples with CC genotype than that in samples with AA and AC genotype. Furthermore, the C allele of HOTTIP rs1859168 could significantly decrease the relative luciferase activity compared to the A allele in three PC cell lines.

Conclusions

The current findings provided evidence that the functional rs1859168 A > C polymorphism may decrease the PC risk by down-regulating the HOTTIP expression.
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Metadata
Title
rs1859168 A > C polymorphism regulates HOTTIP expression and reduces risk of pancreatic cancer in a Chinese population
Authors
Pinghai Hu
Ou Qiao
Jun Wang
Jiao Li
Hao Jin
Zhaolian Li
Yan Jin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2017
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-017-1218-0

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