Association of genetic polymorphisms of CXCL12/SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer.

摘要

BACKGROUND: The aim of this study was to evaluate the relations of chemokine CXCL12, previously known as stromal cell-derived factor-1 (SDF1), and its receptor, CXCR4, gene variants on non-small cell lung cancer (NSCLC) risk and disease severity. METHODS: Through a case-control study design, genomic DNA samples of 247 NSCLC patients and 328 age and sex-matched controls were subjected to polymerase chain reaction-restriction fragment length polymorphism analysis. The validity of this technique was proven by direct sequencing of amplified products. Statistical analyses were conducted to explore the contribution of polymorphism of the CXCL12/SDF1 gene and CXCR4, in the susceptibility to and prognosis of NSCLC. RESULTS: Overall, the genotype frequencies of CXCL12/SDF1 gene and CXCR4, were significantly different between lung cancer patients and controls (p<0.0001), and also different between patients with lung cancers of various stages (p<0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with CXCL12/SDF1 AA (an OR of 1.95, 95% CI 1.08-3.50, p=0.018), or CXCR4 TT (an OR of 4.71, 95% CI 1.99-11.2, p<0.0001), and for individuals with both CXCL12/SDF1 AA and CXCR4 TT genotypes (an OR of 12.4, 95% CI 1.56-98.3, p=0.002). The patients carrying a homologous AA genotype at CXCL12/SDF1, or a homologous TT genotype at CXCR4, had a tendency to advanced disease and toward poorer prognoses compared with other patients. CONCLUSION: A significant association between the polymorphisms of CXCL12/SDF1 and CXCR4, and the susceptibility to and prognosis of NSCLC was demonstrated.