Inherited variants in the chemokine CCL2 gene and prostate cancer aggressiveness in a Caucasian cohort.
OBJECTIVE
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.


METHODS
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 additionally 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.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Tong
T
Sun
Lee Gwo-Shu
LG
Mary
William K
WK
Oh
Matthew L
ML
Freedman
Mark
M
Pomerantz
Kenneth J
KJ
Pienta
Philip W
PW
Kantoff
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018932:Chemokine CCL2 / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012306:Risk
D018932:Chemokine CCL2