ABCB1/MDR1 polymorphism and colorectal cancer risk: a meta-analysis of case-control studies

Abstract

Aim: ABCB1/MDR1 is found in high concentrations on the apical surfaces of colonic epithelial cells. It acts as an efflux pump by transporting toxic endogenous substances, drugs and xenobiotics out of cells. ABCB1/MDR1 polymorphisms may either change its protein expression or alter its function, suggesting a possible association between ABCB1/MDR1 single nucleotide polymorphisms (SNP) and colorectal cancer. Several studies have reported the relationship between ABCB1 gene polymorphism and colorectal cancer (CRC) risk, but no consistent conclusion has been arrived at. We therefore conducted a meta-analysis to identify any association between ABCB1 gene and CRC risk. Method: PubMed, Embase, Google Scholar, Cbmdisc and CNKI were searched for studies on the relationship of ABCB1/MDR1 SNPs and the incidence of CRC. Eligible articles were included for data extraction. The main outcome was the frequency of ABCB1/MDR1 SNPs among cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. Results: There were ten, four and two trials focusing on ABCB1 rs1045642, rs2032582 and rs3789243 SNP respectively. A total of 3175 cases and 3715 controls were included. The meta-analysis, stratified by ethnicity or population source, indicated no association between ABCB1 rs1045642 polymorphism and CRC risk. However, when the study by Bae et al was removed from the analysis, there was some evidence to indicate a higher frequency of T allele in CRC patients among Asians (OR= 1.30, 95%CI 1.02-1.67,P=0.03). Neither ABCB1 rs2032582 nor rs3789243 indicated an association with CRC risk. An increased frequency of only wild-type combined allele (rs2032582G/ rs1045642C) was found in Caucasian patients (OR= 1.22, 95%CI 1.03-1.44, P=0.02). Conclusion: There is some evidence to indicate an association of ABCB1 rs1045642T and CRC risk in Asians. Compared with SNPs for ABCB1 rs1045642, rs2032582 or rs3789243 alone, combined haplotypes of several SNPs might be a better marker to determine the genetic influence on the susceptibility to CRC among Caucasians.