Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver · 2013
Macrophage stimulating protein variation enhances the risk of sporadic extrahepatic cholangiocarcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Krawczyk Marcin, Höblinger Aksana, Mihalache Florentina, Grünhage Frank, Acalovschi Monica, Lammert Frank, Zimmer Vincent
Аннотация
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.
MATERIALS AND 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.
MATERIALS AND 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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overBile Duct NeoplasmsBile Ducts, ExtrahepaticCase-Control StudiesCholangiocarcinomaCholangitis, SclerosingFemaleGene FrequencyGenetic Predisposition to DiseaseHepatocyte Growth FactorHeterozygoteHumansMaleMiddle AgedPolymorphism, Single NucleotideProto-Oncogene ProteinsWhite PeopleYoung Adult