细胞色素 P450（CYP）1A1、1A2 和 2E1 基因的遗传多态性可调节幽门螺杆菌感染患者胃癌的易感性。

Genetic polymorphism of cytochrome P450 (CYP) 1A1, CYP1A2, and CYP2E1 genes modulate susceptibility to gastric cancer in patients with Helicobacter pylori infection.

机构信息

Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India,

出版信息

Gastric Cancer. 2014 Apr;17(2):226-34. doi: 10.1007/s10120-013-0269-3. Epub 2013 May 19.

DOI:10.1007/s10120-013-0269-3

PMID:23686565

Abstract

BACKGROUND

Activity of cytochrome P450 (CYP), a polymorphic carcinogen-activating enzyme, is exaggerated following Helicobacter pylori infection. We studied the role of CYP2E1, CYP1A2 (rs762551), and CYP1A1 (rs4646903) polymorphisms in association with H. pylori infection in gastric carcinogenesis.

METHODS

Genotyping of CYP2E1 (96-bp insertion), CYP1A2 (164A to C), and CYP1A1 (3801C to T) was carried out in 88, 76, 53, and 170 patients with gastric cancer (GC), functional dyspepsia (FD), peptic ulcer (PU), and healthy controls (HC), respectively. Serum IgG antibody (all subjects), rapid urease test, and histology (GC, FD, and PU patients) were used to test for H. pylori.

RESULTS

CYP2E1 gene polymorphism was more common among patients with GC than HC and PU [48/88 (54.5 %) vs. 67/170 (39.4 %); OR 1.9, 95 % CI 1.1-3.2, p = 0.016) and [PU 18/53 (34 %); OR 2.3 (1-4.7), p = 0.02]. CYP1A2 CC or CT genotypes was lower among patients with GC than HC [50/88 (56.8 %) vs. 120/170 (70.6 %); OR 0.54 (0.31-0.92), p = 0.023]. CYP1A1 polymorphism and CYP1A1-CYP1A2 haplotypes were comparable among different groups. CYP2E1 was also more common in patients with GC than HC and PU in the absence of H. pylori [33/60 (55 %) vs. 19/52 (36.5 %); OR 4 (1.5-11.4), p = 0.007 and PU 7/22 (31.8 %); OR 3.4 (1-11.6), p = 0.05]. CYP1A1 (CT + TT) was more common in patients with GC than PU in presence of H. pylori [17/26 (65.4 %) vs. 11/29 (38 %); OR 3.0 (1.03-9.3), p = 0.045].

CONCLUSIONS

The presence of CYP2E1 (96-bp insertion) is associated with increased risk of GC even in absence of H. pylori. CYP1A2 CC or CT is associated with reduced risk of GC.

摘要

背景

细胞色素 P450（CYP）的活性是一种多态致癌原激活酶，在幽门螺杆菌感染后会被夸大。我们研究了 CYP2E1、CYP1A2（rs762551）和 CYP1A1（rs4646903）多态性在与胃癌发生相关的幽门螺杆菌感染中的作用。

方法

分别对 88 例胃癌（GC）、76 例功能性消化不良（FD）、53 例消化性溃疡（PU）和 170 例健康对照（HC）患者的 CYP2E1（96 位插入）、CYP1A2（164A 到 C）和 CYP1A1（3801C 到 T）进行基因分型。所有受试者均进行血清 IgG 抗体检测、快速尿素酶试验和组织学检查（GC、FD 和 PU 患者）以检测幽门螺杆菌。

结果

GC 患者的 CYP2E1 基因突变较 HC 和 PU 患者更为常见[48/88（54.5%）比 67/170（39.4%）；OR 1.9，95%CI 1.1-3.2，p=0.016]和[PU 18/53（34%）；OR 2.3（1-4.7），p=0.02]。GC 患者 CYP1A2 CC 或 CT 基因型较 HC 患者少见[50/88（56.8%）比 120/170（70.6%）；OR 0.54（0.31-0.92），p=0.023]。不同组间 CYP1A1 多态性和 CYP1A1-CYP1A2 单倍型无差异。在不存在幽门螺杆菌的情况下，CYP2E1 在 GC 患者中也比 HC 和 PU 患者更为常见[33/60（55%）比 19/52（36.5%）；OR 4（1.5-11.4），p=0.007 和 PU 7/22（31.8%）；OR 3.4（1-11.6），p=0.05]。在存在幽门螺杆菌的情况下，GC 患者的 CYP1A1（CT+TT）比 PU 患者更为常见[17/26（65.4%）比 11/29（38%）；OR 3.0（1.03-9.3），p=0.045]。