Association of polymorphisms in the genes of the urokinase plasminogen activation system with susceptibility to and severity of non-small cell lung cancer.

Background: Urokinase plasminogen activating (uPA) system is implicated in neoplastic progression. High tissue levels of uPA system components correlate with a poor prognosis in lung cancer. The present study examined the single nucleotide polymorphisms (SNPs) of uPA and the corresponding receptor, uPAR, for exploring their roles in non-small cell lung cancer (NSCLC).

Methods: The allele frequencies and genotype distributions of uPA rs4065 C/T and uPAR rs344781 (-516 T/C) among 375 NSCLC cases and 380 healthy controls were examined using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. Putative association between the above SNPs and clinicopathological characteristics of NSCLC were also analyzed.

Results: The genotype frequencies of the variant homozygotes of uPA and uPAR were significantly different between NSCLC and control subjects. Significant association was also observed between the examined genotypes and disease stage of NSCLC. Logistic regression analysis revealed that individuals with uPA rs4065 TT genotype have higher odds ratios (ORs) for lung cancer. Whereas, subjects with uPAR-344781 CC genotype have lower ORs for lung cancer. The patients carrying a homozygous TT genotype at uPA rs4065, or at least a T allele at uPAR-344781 (-516), had a tendency to develop advanced disease.

Conclusions: Our results revealed that genetic polymorphisms of the uPA rs4065 C/T and uPAR rs344781 (-516 T/C) were associated with the susceptibility and severity of NSCLC.