The Association Between Leptin (-2548 G˃A, rs7799039)/Leptin Receptor (223 A˃G, rs1137101) Polymorphisms and Prostate Cancer

Background: The pathophysiology of Prostate Cancer (PCa) involves a complex interplay of environmental and genetic factors. PCa diagnosis faces challenges of false-positive outcomes, emphasizing the necessity for revising the available screening methods for PCa. Single-nucleotide polymorphisms (SNPs) have been linked with PCa and constitute a key risk factor in prostate carcinogenesis. Objective: This research aimed at examining the association between susceptibility to PCa and polymorphisms of the Leptin (LEP) gene -2548 G˃A (rs7799039) and LEP receptor (LEPR) gene 223 A˃G (rs1137101). Methods: A total of 66 patients and 34 controls of a Jordanian population were recruited. DNA was isolated from blood leucocytes. Polymorphism analyses were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approaches. Results: The mutant allele (A) and genotype (AA) frequencies of the LEP SNP (-2548 G˃A, rs7799039) were significantly higher in the PCa patients (59.1% and 37.9%, respectively) compared to those in the control group (45.6% and 20.6%, respectively) (P = 0.039; OR = 1.88, 95%CI = 1.02 - 2.89 and P = 0.043; OR = 2.86, 95%CI = 1.77 - 5.92, respectively). This indicates that this SNP was associated with an overall increased risk of PCa. In contrast, the LEPR 223 A˃G was not. Further stratification of the PCa group showed that the incidence of both SNPs was correlated with high serum PSA levels and metastasis risk. The results with age and Gleason biopsy score were not conclusive because the trend observed did not reach significance. Conclusions: The findings support our hypothesis regarding the association of the polymorphism in the LEP gene in prostate carcinogenesis (the A and AA frequencies, compared with the control, were associated with a 1.3-fold and a 1.8-fold increased risk for PCa, respectively. However, there was no association between the LEPR (rs1137101) gene variant and PCa risk.