A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.
Isomura
Yoshihiro
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, ISOMURAY-INT@h.u-tokyo.ac.jp
Yamaji
Yutaka
Y
Ohta
Miki
M
Seto
Motoko
M
Asaoka
Yoshinari
Y
Tanaka
Yasuo
Y
Sasaki
Takashi
T
Nakai
Yousuke
Y
Sasahira
Naoki
N
Isayama
Hiroyuki
H
Tada
Minoru
M
Yoshida
Haruhiko
H
Kawabe
Takao
T
Omata
Masao
M
Koike
Kazuhiko
K
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001661:Biliary Tract Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D065731:Cytochrome P-450 CYP2C19; D004067:Digestive System Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19