Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma.
Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.|Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Roongruedee
R
Chaiteerakij
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Brian D
BD
Juran
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Mohammed M
MM
Aboelsoud
Department of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
William S
WS
Harmsen
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Catherine D
CD
Moser
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Nasra H
NH
Giama
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Loretta K
LK
Allotey
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Teresa A
TA
Mettler
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Esha
E
Baichoo
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Xiaodan
X
Zhang
Department of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Terry M
TM
Therneau
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Konstantinos N
KN
Lazaridis
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota.
Lewis R
LR
Roberts
D000368:Aged; D001650:Bile Duct Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D063646:Carcinogenesis / Q000235:genetics*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D015209:Cholangitis, Sclerosing / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D016207:Cytokines; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
Bile duct cancer; biliary tract cancer; gene variant; genetic susceptibility; risk factor