Prognostic assessment of three single-nucleotide polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in extrahepatic cholangiocarcinoma.
OBJECTIVE
Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA.


METHODS
Forty Caucasian patients with extrahepatic CCA and 40 age- and sex-matched healthy white Caucasians were genotyped to elucidate putative associations between clinical outcome and genotypes of the three following SNPs: G protein beta 3 (GNB3) 825C>T, B-cell-lymphoma-2 (Bcl-2) -938C>A, and myeloid cell leukemia-1 (Mcl-1) -386C>G.


RESULTS
Patients homozygous for the C allele of the GNB3 825C>T polymorphism exhibited a significant prolonged overall survival compared with patients displaying the CT or TT genotype (median survival [months]: 31 vs. 13 vs. 7; p < .05) and also showed lower bilirubin serum levels. Additionally, the CC genotype of the BCL2-938C>A polymorphism was associated with higher GLDH serum activities (U/l; 29.8 +/- 7.1 vs. 11.4 +/- 4.3 vs. 5.6 +/- 1.7 comparing CC vs. CA vs. AA; p < .05). Genotype distributions for all SNPs were not significantly different in patients vs. controls.


CONCLUSIONS
GNB3 825C>T SNP may be a novel independent prognostic marker for patients suffering from extrahepatic CCA with the CC genotype to be associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and reveal additional functional SNP effects.
Fingas
Christian Dominik
CD
Department of Gastroenterology and Hepatology, University Hospital of Essen, Germany.
Katsounas
Antonios
A
Kahraman
Alisan
A
Siffert
Winfried
W
Jochum
Christoph
C
Gerken
Guido
G
Nückel
Holger
H
Canbay
Ali
A
D000367:Age Factors; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality; D017734:Bile Ducts, Extrahepatic; D014408:Biomarkers, Tumor / Q000378:metabolism; D015992:Body Mass Index; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D014408:Biomarkers, Tumor; C454420:G-protein beta3 subunit; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D020962:Heterotrimeric GTP-Binding Proteins