Stromal cell-derived factor-1 but not its receptor, CXCR4, gene variants increase susceptibility and pathological development of hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide. Genetic polymorphism has been reported as a predictive factor related to a higher risk for HCC. Because the stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have been reported to play important roles in tumor cell proliferation, angiogenesis, and metastasis of HCC, the aim of this study was to estimate the relationship between SDF-1 and CXCR4 gene variants to HCC risk and clinicopathological status. Methods: Polymerase chain reaction-restriction fragment length polymorphism was used to measure SDF-1 (rs1801157) and CXCR4 (rs2228014) gene polymorphisms in 311 healthy controls and 102 patients with HCC. Results: Compared to controls, individuals with at least one A allele had a higher risk of 1.57-fold (95% CI: 1.00-2.47) to induce HCC and had a risk of 2.81-fold (95% CI: 1.04-7.58) to develop a status of stage III or stage IV disease, after being adjusted for other confounders. However, there was no significant association between CXCR4 gene polymorphism and either HCC risk or pathological status. Additionally, both gene polymorphisms were not associated with the serum expression of liver-related clinical pathological markers. Conclusions: SDF-1-3′A gene polymorphism could be considered as a factor related to an increased susceptibility to the risk and pathological development of HCC. © 2009 by Walter de Gruyter Berlin New York.