Association study between KCNQ1 and KCNQ1OT1 genetic polymorphisms and gastric cancer susceptibility and survival in a Chinese Han population: a case-control study

Abstract

BACKGROUND: The present study analyzed gene polymorphisms in the potassium voltage-gated channel KQT-like subfamily member 1 (KCNQ1) and the long noncoding RNA, KCNQ1OT1, and their impacts on genetic susceptibility and survival in a Chinese Han population with gastric cancer (GC). METHODS: We designed a case-control study that included 681 patients with GC and 756 healthy controls. Three single-nucleotide polymorphisms (SNPs) in the KCNQ1 gene region and eight SNPs in the KCNQ1OT1 gene region were selected for further research. RESULTS: Among the 11 SNPs, we found no significant differences in the genotype and allele frequencies between GC patients and the healthy population. Hierarchical analysis by the log-additive model indicated that the KCNQ1 rs231348 CT genotype was significantly associated with an increased GC risk in individuals aged ≥55 years, regardless of gender. The KCNQ1OT1 rs231352 CC and rs7128926 AA genotypes increased the risk of GC in individuals with stage III/IV tumors larger than 5 cm in diameter. On evaluating the genotype polymorphism and survival analysis, we detected that the AA genotypes of the KCNQ1OT1 rs7128926 and rs7939976 polymorphisms presented a significant survival advantage over the GA/GG genotypes, especially in patients with the following characteristics: age >55, Helicobacter pylori infection, BMI >24, tumor in the non-cardia region with a diameter greater than 5 cm, clinical stage II, and postoperative adjuvant chemotherapy. CONCLUSIONS: Our results suggest that the KCNQ1 rs231348 and KCNQ1OT1 rs231352 polymorphisms might be independent predictors of the risk of GC susceptibility depending on certain factors, such as the age of the individual and the tumor stage and diameter. Simultaneously, genotype polymorphism of the rs7128926 and rs7939976 loci of the KCNQ1OT1 gene independently predicted the recurrence-free survival (RFS) and overall survival (OS) of GC patients.