Association of the c.3972C>T Variant of the Multidrug Resistance-Associated Protein 2 Gene (MRP2/ABCC2) with Susceptibility to Bile Duct Cancer

Abstract

BACKGROUND: Multidrug resistance-associated protein 2 (MRP2/ABCC2) is one of the ATP-binding cassette (ABC) transporters expressed on the apical membrane of hepatocytes and cholangiocytes. ABCC2 plays an important role in the biliary clearance of endogenous and exogenous toxic compounds. Recently, the ABCC2 variant c.3972C>T in exon 28 has been shown to be associated with hepatocellular carcinoma risk. Our aim was to assess the role of this ABCC2 variant on cholangiocarcinoma susceptibility. METHODS: Prospectively, we recruited 60 cholangiocarcinoma patients and 73 healthy controls of Caucasian origin. The c.3972C>T polymorphism was genotyped using solution-phase hybridization reactions with 5'-nuclease and fluorescence detection (TaqMan assays). RESULTS: Allele frequencies were in Hardy-Weinberg equilibrium (p > 0.05). The c.3972T allele was significantly more frequent in patients with cholangiocarcinoma (39.2%) compared to healthy controls (26.0%, p = 0.022), resulting in an odds ratio (OR) of 1.83 (95% CI = 1.09-3.08). Armitage's trend test showed a significant association between genotypes and cancer susceptibility (p = 0.026, OR = 1.95). CONCLUSIONS: We describe a novel association between the common ABCC2 variant c.3972C>T and cholangiocarcinoma risk. Further studies are warranted to replicate our findings in different populations and to elucidate the mechanisms of this observation.