Abstract
AIM: Although the role of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers has been documented, the association between polymorphisms of LEPR gene and lung cancer remains unknown. METHOD: We recruited 744 patients histologically diagnosed as non-small cell lung cancer (NSCLC) and 832 controls in this study. Polymorphism analysis of LEPR gene was performed by PCR-restriction fragment length polymorphisms. RESULTS: The Arg/Arg genotype and Arg allele frequency of the Gln223Arg in LEPR gene were significantly prevalent in NSCLC subjects than in controls (P < 0.05). The odd ratio (OR) for NSCLC in Arg/Arg genotype carriers was 3.12 (95% CI: 2.25-4.56, P = 0.0023, with Gln/Gln as reference). There were no significant differences in the genotype distributions and allele frequencies of Lys109Arg and Lys656Asn in LEPR gene between NSCLC cases and controls (All P > 0.05). The Arg/Arg carriers had higher cancer grade and higher TNM stage. Kaplan-Mier curve showed the Arg/Arg carriers had a poor prognosis than those with Gln/Arg and Gln/Gln genotype carriers. Cox proportional hazards regression models showed the hazard ratio (HR) for death associated with Arg/Arg genotype was 3.43 (95% CI: 2.45-5.92, compared with Gln/Gln carriers, P = 0.002). The other two SNPs of LEPR gene did not show this trend in the evaluation of their role in determining the prognosis of NSCLC subjects. CONCLUSION: The results suggest the polymorphisms of Gln223Arg, rather than Lys109Arg and Lys656Asn, may be used as a molecular marker for progression and prognosis of NSCLC.