Open AccessAssociation between variants in inflammation and cancer‐associated genes and risk and survival of cholangiocarcinoma
Author(s) -
Chaiteerakij Roongruedee,
Juran Brian D.,
Aboelsoud Mohammed M.,
Harmsen William S.,
Moser Catherine D.,
Giama Nasra H.,
Allotey Loretta K.,
Mettler Teresa A.,
Baichoo Esha,
Zhang Xiaodan,
Therneau Terry M.,
Lazaridis Konstantinos N.,
Roberts Lewis R.
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.501
Subject(s) - single nucleotide polymorphism , snp , proportional hazards model , carcinogenesis , genotype , candidate gene , biology , oncology , medicine , survival analysis , genetic association , logistic regression , genetics , cancer , bioinformatics , gene
Genetic risk factors for cholangiocarcinoma ( CCA ) remain poorly understood. We assessed the effect of single‐nucleotide polymorphisms ( SNP s) 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 SNP s in nine genes were genotyped. The log‐additive genotype effects of SNP s 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 SNP s 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.