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A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer
- Source :
- Journal of Gastroenterology. 45:1045-1052
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- Cytochrome P450 2C19 (CYP2C19) is clinically important for the metabolism of many therapeutic drugs. CYP2C19 has two main point mutation sites leading to low metabolic capacity. Several CYP enzymes are also important for the metabolism of chemical carcinogens, and several studies have reported associations between CYP polymorphism and cancer susceptibility. Speculating on a potential association between CYP2C19 polymorphism and cancer susceptibility, we conducted this study in two phases. Cell lines of various gastroenterological cancers were screened in the first phase. A clinical investigation was then conducted to confirm the association with the candidate cancer in the second phase. Genetic polymorphism of CYP2C19 was investigated in a total of 114 cell lines of five gastroenterological cancers. Based on this screening investigation suggesting an association with biliary tract cancer, we conducted a related study by recruiting 65 patients with biliary tract cancer and 566 patients with benign diseases as controls. Among the 114 cell lines investigated, biliary tract cancer was suggested to be most strongly associated with poor metabolizers of CYP2C19. Among 65 patients with biliary tract cancer, 18 (28%) were poor metabolizers of CYP2C19, whereas 87 (15%) of 566 control patients were poor metabolizers. The age- and gender-adjusted odds ratios for intermediate and poor metabolizers regarding the risk of biliary tract cancer were 1.5 (95% CI: 0.8–3.0, P = 0.17) and 2.7 (1.3–5.9, P = 0.006) compared to extensive metabolizers. A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.
- Subjects :
- Adult
Male
medicine.medical_specialty
Pathology
Single-nucleotide polymorphism
CYP2C19
Biology
Digestive System Neoplasms
Gastroenterology
Surgical oncology
Cell Line, Tumor
Internal medicine
Genotype
medicine
Humans
Genetic Predisposition to Disease
Allele
Aged
Polymorphism, Genetic
Haplotype
Odds ratio
Middle Aged
Hepatology
Cytochrome P-450 CYP2C19
Biliary Tract Neoplasms
Case-Control Studies
Female
Aryl Hydrocarbon Hydroxylases
Subjects
Details
- ISSN :
- 14355922 and 09441174
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....cfde887e929fc239bd2b75d731ca4496