Associations of THBS2 and THBS4 polymorphisms to gastric cancer in a Southeast Chinese population

Abstract

Thrombospondin-2 (THBS2) and Thrombospondin-4 (THBS4) play an important role in cancer development and progression. However, genetic evidence for their roles in gastric cancer (GC) is lacking. The aim of this study was to explore the association of THBS2/THBS4 polymorphisms with risk and clinicopathological features of GC in a Southeast Chinese population. Eight tagging SNPs in THBS2 and THBS4 were genotyped in 761 GC cases and 739 controls from Chinese case-control sets using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. THBS2/THBS4 mRNA expression was studied in 82 human GC tumors and in mouse stomach tissues by real-time PCR. We found that both THBS2 and THBS4 were abundantly expressed in mouse stomach. THBS4 mRNA expression in human stomach was associated with tumor size (P = 0.002) and tumor-node-metastasis (TNM) (P = 0.010), and THBS2 mRNA expression was associated with the TNM (P = 0.010). Patients with the rs77878919^AG genotype were more prone to developing diffuse-type GC. THBS4 SNPs (rs77878919 and rs7736549) had a modest cumulative effect on the risk of poor prognosis (TNM), with that risk in the highest trend for patients carrying both these unfavorable genotypes. In addition, individuals carrying the THBS4 rs10474606 variant homozygous AA had a modest reduced GC risk. We conclude that THBS2/THBS4 may be functional in playing important role in GC, which was supported by the evidence of the mRNA overexpression in GC and the modest associations of THBS2/THBS4 polymorphisms to GC. These findings might be useful for risk assessment and prognosis prediction of GC.