Abstract

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.

Links

Publisher Full Text

Authors

Singh V, Srivastava P, Srivastava N, Kapoor R, Mittal RD

Institution

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014 Uttar Pradesh, India.

Source

Molecular biology reports 39:10 2012 Oct pg 9827-34

MeSH

BCG Vaccine
Cancer Vaccines
Case-Control Studies
Chemokine CCL2
Disease-Free Survival
Epistasis, Genetic
Female
Genetic Association Studies
Haplotypes
Humans
India
Kaplan-Meier Estimate
Male
Membrane Proteins
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Polymorphism, Single Nucleotide
Population
Receptors, CCR2
Tumor Suppressor Proteins
Urinary Bladder Neoplasms

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22733495