A functional genetic variant in GAS5 lncRNA (rs145204276) modulates p27 Kip1 expression and confers risk for gastric cancer.

OBJECTIVE: There has been extensive progress in the identification of single nucleotide polymorphisms (SNPs) affecting susceptibility to gastric cancer in recent years. We hypothesised a functional polymorphism (rs145204276) in GAS5 lncRNA (growth arrest specific transcript 5 long noncoding RNA) in gastric cancer that may modulate the p27Kip1 protein level.

MATERIAL AND METHODS: We recruited 130 gastric cancer cases and 230 age and sex matched healthy control subjects. Genotyping was performed by tetra-primer amplification refractory mutation system-polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. Expression of p27Kip1 protein was evaluated in gastric cancer tissues by ELISA.

RESULTS: The frequencies of the ins/ins, ins/del and del/del genotypes were 67.7%, 27.7% and 4.6% in cases and 54.8%, 36.5% and 8.7% in controls, respectively (p=0.045). The del allele carriers seemed to confer protective effects on gastric cancer risk (OR=0.58; 95%CI= 0.41-0.83; P=0.01). Patients with the del/del genotype showed higher levels of p27Kip1 than patients with the ins/ins genotype (P<0.001).

CONCLUSIONS: In conclusion, genetic polymorphism of GAS5 may influence the development of gastric cancer and so could be a new marker of this disease. The link with disease may involve p27Kip1 expression.