The role of chemokine and chemokine receptor gene variants on the susceptibility and clinicopathological characteristics of bladder cancer

The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3′A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population.The genotyping was done by PCR and PCR-Restriction Fragment Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients and 197 controls.The SDF-1 3′AA genotype conferred significantly increased susceptibility to BC. The carriers with AA genotype or at least one A allele of CCR2 had an increased risk of developing BC. CCR5 wt/Δ32 genotype and CCR5 Δ32 allele were also observed to be involved in the susceptibility to BC. Additionally, the combination of CCR2 V64I and CCR5 Δ32 (i.e., GG-wt/Δ32) was found to be associated with BC risk. With respect to the stage of BC, the AA genotype of SDF-1 and at least one T allele of CXCR4 were significantly associated with high T stage as compared to GG genotype of SDF-1 and CC genotype of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of CCR2 had an increased risk of high grade and stage tumors as compared to those with GG genotype.Our results suggest that the genetic variants of SDF-1 3′A, CCR2A V64I and CCR5 Δ32 gene polymorphisms may modify the BC risk. Furthermore, SDF-1 3′A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to the muscle invasive BC in a Turkish population.

► The first study on the role of these six gene polymorphisms with bladder cancer risk
► SDF1, CCR2 and CCR5Δ32 gene polymorphisms may be risk factors for bladder cancer.
► SDF1, CCR2, CXCR4 gene variants may contribute to the progression of the disease.
► The combination of CCR2 and CCR5Δ32 genes may increase the risk for bladder cancer.