Functional variants of lncRNA LINC00673 and gastric cancer susceptibility: A case-control study in a Chinese population

Abstract

Background: 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.