Cancer Management and Research (May 2019)
Functional variants of lncRNA LINC00673 and gastric cancer susceptibility: a case-control study in a Chinese population
Abstract
Kexin Zhao,1 Rui Zhang,2 Tiantian Li,3 Zhifan Xiong11Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, People’s Republic of China; 2The Second Clinical Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3College of Life Science & Technology, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of ChinaBackground: Two genome-wide association studies (GWASs) identified LINC00673 rs11655237 was associated with susceptibility to pancreatic cancer.Methods: To investigate the association between LINC00673 polymorphisms and gastric cancer (GC) risk, and the impact of gene-environmental interaction on GC risk, we conducted this case-control study in a Chinese population.Results: We found rs11655237 significantly increased susceptibility of GC in the Chinese population (OR=1.29; 95% CI=1.12–1.48; P=4.1×10−4,), and a significant interaction was found between rs11655237 and Helicobacter pylori infection (P=0.006). Expression of LINC00673 was significantly higher in adjacent normal tissues than in paired cancer tissues (P<0.001) and significantly lower in the cancer or paired adjacent normal tissues of GC patients with rs11655237 allele A than in those with rs11655237 allele G (P<0.001). Mechanism exploration found that, the construct with the rs11655237[A] allele had significantly reduced luciferase activity in the presence of miR-1231, and this effect could be completely rescued when miR-1231 inhibitor was present.Conclusion: Our results indicate that LINC00673 rs11655237 is associated with an increased GC risk, possibly by down-regulating LINC00673 expression through creating a miR-1231 binding site.Keywords: gastric cancer, LINC00673, genetic, rs11655237, polymorphism