Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

Background: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancershave been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma(CC-RCC) remains unknown. The aim of this study was to explore any relation. Materials and
Methods: Thestudy population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analysesof Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment lengthpolymorphism approaches respectively.
Results: Comparisons of allelic and genotypic frequencies in Lys109Argand Gln223Arg showed no significant difference between the cases and controls. However, when evaluating thecombined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30)and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could notbe calculated for a value of zero) . Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg inthe cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in thecases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter couldnot be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele(d’=0.9399) in the CC-RCC subjects, but not in the controls.
Conclusions: Our data suggest that the GG/GGcombined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCCrisk.