title: Genetic variants of chemokine CCL2 and chemokine receptor CCR2 genes and risk of prostate cancer.
abstract: Chemokines and their receptors acts as mediators of migration of immune cells to the site of inflammation and deregulated inflammatory response is associated with increased risk of cancer. We performed a case-control study to analyze the frequencies of CCL2 (I/D, rs3917887), -2518 (A > G, rs1024611), and CCR2 (G > A, rs1799864) polymorphisms for prostate cancer (PCa) risk. In this hospital-based case-control study, histologically confirmed 195 PCa patients and 250 unrelated healthy controls of similar ethnicity were genotyped by PCR-RFLP. The result showed that heterozygous ID (odds ratio (OR) = 1.71; p = 0.010) carrier genotype of CCL2 gene were at increased risk for developing PCa. Variant allele D carriers (ID + DD) demonstrated a 1.67-fold increased risk (OR = 1.67; p = 0.010), suggesting a dominant effect model involved in PCa risk. Similarly, variant allele D of CCL2 gene also had a higher risk (OR = 1.53; p = 0.040) for developing PCa. High risk to PCa was also observed with respect to diplotypes, I-G (OR = 1.83; Bonferroni corrected p value (P c) = 0.004) and D-A (OR = 2.11; P c = 0.004) of CCL2 I/D and -2518 (A > G). In association of genotypes with clinic-pathological grade of tumor, homozygous DD (OR = 7.40; P c = 0.042) and variant allele carrier ID + DD (OR = 2.42; P c = 0.036) genotypes of CCL2 gene conferred risk in high Gleason grade tumor of PCa. We observed a significantly enhanced risk for PCa due to interaction between CCL2 I/D, -2518 (A > G), and CCR2 (G > A) genotypes. However, -2518 (A > G) and CCR2 V64I (G > A) gene polymorphisms were not significantly associated with PCa risk. Our results supported that CCL2 I/D gene variant contribute to the susceptibility and clinic-pathological characteristic of PCa and could be considered as an important risk factor for this malignancy in North Indian men.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Raju K
authors.initials: RK
authors.lastname: Mandal
authors.forename: Toshi
authors.initials: T
authors.lastname: Agrawal
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D004843:Epistasis, Genetic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics*; D012306:Risk
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2