Inherited variants in the chemokine CCL2 gene and prostate cancer aggressiveness in a caucasian cohort

Purpose: Though C-C chemokine ligand 2 (CCL2) has been shown to play a pivotal role in prostate cancer tumorigenesis and invasion, the role of inherited variation in the CCL2 gene in prostate cancer progression and metastases remains unanswered. This study is aimed to determine the influence of CCL2 germline variants on prostate cancer aggressiveness. Experimental Design: We performed an association study between six single nucleotide polymorphisms (SNP) in the CCL2 gene and prostate cancer clinicopathologic variables in a large hospital-based Caucasian patient cohort (N = 4,073). Results: Genetic variation at CCL2 is associated with markers of disease aggressiveness. Three SNPs, each in strong linkage disequilibrium, are associated with a higher (>7) biopsy Gleason score: CCL2 -1811 A/G, -2835 A/C, and +3726 T/C (P = 0.01, 0.03, and 0.04, respectively). The CCL2 -1811 G allele is addionally associated with advanced pathologic stages in patients who underwent radical prostatectomy (P=0.04). In haplotype analysis, we found that the frequency of a common haplotype, H5, was higher among patients with D'Amico good risk features (P_permutation = 0.04). Conclusions: These results support the influence of CCL2 variants on prostate cancer development and progression.