title: Macrophage stimulating protein variation enhances the risk of sporadic extrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Primary sclerosing cholangitis confers risk of cholangiocarcinoma. Here, we assessed the primary sclerosing cholangitis-associated variant rs3197999 in the MST1 gene, coding for RON receptor tyrosine kinase ligand macrophage stimulating protein, in a large European cholangiocarcinoma cohort.
  
  
  METHODS
  223 cholangiocarcinoma patients including three primary sclerosing cholangitis individuals and 355 cancer- and primary sclerosing cholangitis-free controls were genotyped for MST1 rs3197999.
  
  
  RESULTS
  The cancer group departed from Hardy-Weinberg equilibrium (p = 0.022) and exhibited a trend for rs3197999 [A] overrepresentation (31% vs. 26%: p = 0.10). Homozygous rs3197999 [AA] carrier status significantly increased overall (OR = 1.97; p = 0.023) and primary sclerosing cholangitis-unrelated biliary tract cancer risk (OR = 1.84; p = 0.044), relative to homozygous common allele carriers. The association was most pronounced in patients with extrahepatic tumours. This finding was robust to multivariate analysis (p < 0.05), validating the [AA] genotype as an independent cholangiocarcinoma risk factor.
  
  
  CONCLUSIONS
  These results suggest that the [AA] genotype of the common MST1 variant rs3197999 enhances genetic risk of sporadic extrahepatic cholangiocarcinoma irrespective of primary sclerosing cholangitis status, presumably by modulating inflammatory responses and/or altered MSP/RON signalling.
authors: Department of Medicine II, Saarland University Medical Center, 66421 Homburg, Germany. marcin.krawczyk@uks.eu
authors: Marcin
authors: M
authors: Krawczyk
authors: Aksana
authors: A
authors: Höblinger
authors: Florentina
authors: F
authors: Mihalache
authors: Frank
authors: F
authors: Grünhage
authors: Monica
authors: M
authors: Acalovschi
authors: Frank
authors: F
authors: Lammert
authors: Vincent
authors: V
authors: Zimmer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000150:complications / Q000235:genetics*; D017734:Bile Ducts, Extrahepatic; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000235:genetics*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor