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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Purpose

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.

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Conflict of interest statement

There was no conflict of interest in this study.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Yoshihiro Isomura, Yutaka Yamaji, Motoko Seto, Yoshinari Asaoka, Yasuo Tanaka, Takashi Sasaki, Yousuke Nakai, Naoki Sasahira, Hiroyuki Isayama, Minoru Tada, Haruhiko Yoshida, Takao Kawabe & Kazuhiko Koike

  2. Department of Gastroenterology, Sanno Hospital, 8-10-16 Akasaka, Minato-Ku, Tokyo, 107-0052, Japan

    Miki Ohta

  3. Department of Gastroenterology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanasi, 400-8506, Japan

    Masao Omata

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  1. Yoshihiro Isomura
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  2. Yutaka Yamaji
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  14. Masao Omata
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  15. Kazuhiko Koike
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Correspondence to Yoshihiro Isomura.

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Isomura, Y., Yamaji, Y., Ohta, M. et al. A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer. J Gastroenterol 45, 1045–1052 (2010). https://doi.org/10.1007/s00535-010-0246-0

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  • DOI: https://doi.org/10.1007/s00535-010-0246-0

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