title: Genetic polymorphism of cytochrome P450 (CYP) 1A1, CYP1A2, and CYP2E1 genes modulate susceptibility to gastric cancer in patients with Helicobacter pylori infection.
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.
authors.affiliation: Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India, ujjalaghoshal@yahoo.co.in.
authors.forename: Ujjala
authors.initials: U
authors.lastname: Ghoshal
authors.forename: Shweta
authors.initials: S
authors.lastname: Tripathi
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
authors.forename: Dipti
authors.initials: D
authors.lastname: Chourasia
authors.forename: Niraj
authors.initials: N
authors.lastname: Kumari
authors.forename: Narendra
authors.initials: N
authors.lastname: Krishnani
authors.forename: Uday C
authors.initials: UC
authors.lastname: Ghoshal
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010437:Peptic Ulcer / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2