Association of inflammatory chemokine gene CCL2I/D with bladder cancer risk in North Indian population.
Chemokine genes have been proposed as good candidate genes for conferring susceptibility to Bladder cancer (BC). We examined the combined effect of multiple alleles of pro inflammatory chemokine genes for determining the risk of BC. We tested association of three gene polymorphisms of CCL2I/D (rs3917887), CCL2A2518G (rs1024611) and CCR2V64I (rs1799864) with BC risk in North Indian population. Genotypes were assessed in hospital-based case-control study comprising of 200 BC patients and 200 healthy controls. Genomic DNA was isolated from blood and genotyping done using PCR-RFLP method. In CCL2I/D polymorphism, the heterozygous genotype (I/D) showed high risk of BC p < 0.001 OR = 2.56 and combination of ID + DD showed significant high risk for BC (p = 0.001 OR = 2.12). Haplotype analysis of CCL2I/D, CCL2A2518G gene polymorphisms demonstrated that combination of D-A was associated with 1.5-fold increased risk of BC. Variant genotype (DD) of CCL2I/D gene was associated with high risk of recurrence (p < 0.001 HR = 15.18) in superficial BC patients receiving BCG treatment thus showing least survival (log rank = 0.019). Our study suggested CCL2I/D polymorphism to be associated with higher BC risk and no contribution of CCR2V64I and CCL2A2518G genes. However, study with large sample size and diverse ethnicity is required to validate our observations.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014 Uttar Pradesh, India.
Vibha
V
Singh
Priyanka
P
Srivastava
Neena
N
Srivastava
Rakesh
R
Kapoor
Rama Devi
RD
Mittal
D001500:BCG Vaccine / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D018572:Disease-Free Survival; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D011153:Population; D054390:Receptors, CCR2 / Q000235:genetics; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy
D001500:BCG Vaccine; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D019496:Cancer Vaccines; D018932:Chemokine CCL2; D008565:Membrane Proteins; D054390:Receptors, CCR2; C449281:TMEM158 protein, human; D025521:Tumor Suppressor Proteins