Association between gastric mucosal glutathione-S-transferase activity, glutathione-S-transferase gene polymorphisms and Helicobacter pylori infection in gastric cancer

Indian J Gastroenterol. 2011 Dec;30(6):257-63. doi: 10.1007/s12664-011-0144-2. Epub 2011 Dec 3.

Abstract

Aim: Helicobacter pylori infection, though common, leads to gastric cancer (GC) in less than 1% individuals, suggesting the role of host factors. We previously reported the role of glutathione-S-transferase (GST) polymorphisms, the gene encoding a carcinogen-detoxifying enzyme, in GC. This study was aimed to evaluate GST enzyme activity, GST polymorphism, glutathione (GSH) levels and H. pylori in patients with GC.

Methods: GST and GSH levels were estimated in gastric biopsies of 52 patients with GC, 37 functional dyspepsia (FD) and 39 peptic ulcer (PU), and correlated with H. pylori (ELISA) infection and GST polymorphisms. GST polymorphisms were separately analyzed in relationship to H. pylori in 82 GC, 72 FD, 53 PU and 89 healthy controls (HC).

Results: GST activity was lower in patients with GC in comparison to PU (p = 0.03), but GSH levels were comparable. GSTT1 null genotype (GSTT1*0) and simultaneous deletion of both GSTT1 and GSTM1 genes was associated with lower enzyme activity (p = 0.02 and 0.01, respectively). GST and GSH levels in H. pylori positive and negative patients with GC, FD and PU were comparable. Presence of H. pylori infection along with GSTT1*0 (p = 0.006) and GSTM1*0 (p = 0.05) was associated with lower enzyme activity. GSTT1*0 was associated with higher odds ratio (OR) of GC in presence of H. pylori (GC vs. HC: p = 0.02, OR 2.6 [95% CI = 1-6] vs. p = 0.7, 1.3 [0.4-5.0]; GC vs. PU: p = 0.04, OR 3 [95% CI = 1-9] vs. not applicable (OR could not be computed as frequency of GSTT1*0 in H. pylori negative patients with PU was zero)].

Conclusions: GC is associated with reduced GST activity. Odds ratio of GC associated with GSTT1*0 is enhanced in presence of H. pylori probably due to combined effect of both on enzyme activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Female
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / pathology
  • Glutathione Transferase / genetics*
  • Helicobacter Infections / enzymology
  • Helicobacter Infections / genetics
  • Helicobacter Infections / pathology
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Male
  • Metabolic Detoxication, Phase II / genetics*
  • Middle Aged
  • Odds Ratio
  • Peptic Ulcer / enzymology
  • Peptic Ulcer / genetics
  • Peptic Ulcer / pathology
  • Polymorphism, Genetic
  • Stomach Neoplasms* / enzymology
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology

Substances

  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1