Genetic polymorphisms in the osteopontin promoter increases the risk of distance metastasis and death in Chinese patients with gastric cancer

BACKGROUND: In vitro and in vivo studies have suggested that osteopontin (OPN) is associated with many types of cancers. However, no studies have reported the incidence of OPN polymorphisms and the risk of gastric cancer. The aim of this study was to investigate the association between OPN polymorphisms and gastric cancer in a Chinese patient population. METHODS: Three genetic variants in the OPN promoter were genotyped using direct sequencing in 200 gastric cancer patients and 200 gender- and age-matched cancer-free controls. The 4-year survival curve was calculated using the Kaplan-Meier method and compared using the log-rank test for each single nucleotide polymorphism (SNP) site. We measured the promoter activity of the -443 T → C polymorphism using a dual luciferase reporter assay. RESULT: For the variant at nt -443 (CC), there was a significant difference between the number of patients with stage IV and those with stage I gastric cancer (IA + IB; P = 0.014) and between those with stage IV and all other stages of gastric cancer (IA + IB + II + III; P = 0.02). For the variant at nt -443 (CT), there was a significant difference between the number of gastric cancer patients with stage IV and those with stage II (P = 0.013). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). Moreover, significantly higher luciferase activities were observed in the pGL3-C construct compared to the pGL3-T construct. CONCLUSIONS: This study provides the first evidence that variation at nt -443 in the OPN promoter increases the potential for gastric cancer metastasis and subsequent death in the Chinese population.