Z Gastroenterol 2014; 52 - KG098
DOI: 10.1055/s-0034-1386120

Common genetic variants in the bile salt export pump ABCB11 and genetic susceptibility to cholangiocarcinoma

V Zimmer 1, A Höblinger 2, M Acalovschi 3, F Lammert 4
  • 1Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Homburg, Germany
  • 2Universitätsklinik Bonn, Bonn, Germany
  • 3University Iuliu Hatieganu, Cluj-Napoca, Romania
  • 4Universitätsklinikum des Saarlandes, Homburg, Germany

Background: Though representing the second most common primary liver cancer, the pathogenesis of cholangiocarcinoma (CCA) is insufficiently characterized. The combined effects of cholestasis and chronic inflammation are proposed to be key factors in CCA development. However, reliable information on inherited risk factors underlying CCA susceptibility is limited, genetic variation in hepatobiliary transporters has been suggested to modulate genetic risk.1 Therefore we now extended our previous work to ABCB11 rs3815676 and rs7577650 recently associated with intrahepatic cholestasis of pregnancy (ICP).2

Patients and methods: Overall, 220 individuals with CCA (males n = 130, age 66.1 ± 11.9 years) originating from Germany and Romania were genotyped. The control group consisted of 300 CCA- and PSC-free individuals (males n = 131, age 60.7 ± 10.9 years). The common single nucleotide polymorphisms (SNPs) in the bile salt export pump ABCB11 rs3815676 and rs7577650 were genotyped by PCR-based assays with 5'-nuclease and fluorescence detection (TaqMan).

Results: All genotype frequencies were in Hardy-Weinberg equilibrium (p > 0.05). The association tests do not provide evidence for genetic risk modulation by either ABCB11 variant: rs3815676, odds ratio (OR)= 0.67; rs7577650, OR = 1.06; all p > 0.05.

Conclusions: Despite the strong functional candidacy, our data do not support a prominent role of the common ABCB11 variants recently implicated in ICP on genetic CCA risk. Of note, our previous work did not replicate the reported association of ABCB11 A444V and genetic CCA risk (unpublished data). However, taking into account data from paediatric cohorts and recent reports on CCA occurrence in families with ABCB4 mutations, resequencing of candidate gene loci appears warranted to adequately fully assess the potential contribution of hepatobiliary transporter variation on CCA susceptibility.3,4

References:

1. Wadsworth et al. Dig Dis 2011

2. Dixon et al. Am J Gastro 2014

3. Strautnieks et al. Gastroenterology 2008

4. Tougeron et al. J Hepatol 2012