Sugimoto M, Furuta T, Shirai N, Nakamura A, Kajimura M, Sugimura H, Hishida A, Ishizaki T
First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Aliment Pharmacol Ther. 2005 Nov 15;22(10):1033-40. doi: 10.1111/j.1365-2036.2005.02678.x.
Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s).
To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared.
Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased.
In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.
细胞色素P450 2C19（CYP2C19）基因多态性与肺癌、肝癌或食管癌的发生有关，其机制可能是通过对致癌物的解毒作用或对前致癌物的激活作用。
阐明CYP2C19基因多态性与日本人群胃癌发生之间的关联。方法：我们测定了111例幽门螺杆菌阳性的胃癌患者以及315例幽门螺杆菌阳性的非胃癌对照者（仅患有胃炎或消化性溃疡的患者）的CYP2C19基因型（CYP2C19*1、2和3）。比较了胃癌患者和对照者中CYP2C19基因型的频率以及血清胃蛋白酶原I和II水平（胃萎缩的生物标志物）。
纯合子广泛代谢型、杂合子广泛代谢型和慢代谢型在胃癌患者中的频率分别为31.5%、42.3%和26.2%，在对照者中的频率分别为38.1%、47.0%和14.9%（P = 0.046）。慢代谢型与胃癌发生风险增加相关，年龄和性别校正后的比值比（OR）为1.975 [95%置信区间（CI）：1.068 - 3.649]，尤其是弥漫型（OR：3.385，CI：1.187 - 9.648）。CYP2C19基因型与血清胃蛋白酶原I水平或胃蛋白酶原I / II比值之间无显著关联，尽管胃癌患者的血清胃蛋白酶原I水平显著降低。
在幽门螺杆菌阳性的日本人中，CYP2C19慢代谢型似乎患胃癌的风险增加，尤其是弥漫型，可能需要加强随访以仔细检查是否可能发生胃癌。
