Association of EcoRI polymorphism of the metastasis-suppressor gene NME1 with susceptibility to and severity of non-small cell lung cancer

Background: Human lung cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. However, the biallelic EcoRI polymorphism of this gene has not been studied in lung cancer. With this allelic association study, we aimed to investigate the impact of polymorphisms of the NME1 gene on the susceptibility to and severity of non-small cell lung cancer (NSCLC). Methods: Through a case-control study design, genomic DNA samples of 255 NSCLC patients and 303 controls, who were age and sex-matched and recruited from the health check-up unit, were subjected to polymorphism analysis with polymerase chain reaction-restriction fragment length polymorphism technique. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of the metastasis-suppressor gene NME1 in the susceptibility to and severity of NSCLC. Results: Overall, the genotype frequencies of NME1 gene 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 in patients homozygous (+/+) for variant allele (an OR of 4.02, 95% CI 2.39-6.76; p < 0.0001). Patients carrying a variant polymorphic homozygote (+/+) also had a tendency to advanced disease (p = 0.001). Conclusion: A significant association between the polymorphisms of NME1 gene and the susceptibility to and severity of lung cancer was demonstrated.