The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients

Abstract

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. 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. 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. 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.