title: Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer.
abstract: OBJECTIVE
  To evaluate how Helicobacter pylori (H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.
  
  
  METHODS
  This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori IgG seropositivity. Exposure to H. pylori was determined by IgG seropositivity which was detected by enzyme linked immunoassay (ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.
  
  
  RESULTS
  Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased (controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased (controls vs patients; seronegative: 52.85 ± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls (P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups (rs = 0.494, P = 0.0001 and rs = 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls (controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.
  
  
  CONCLUSIONS
  A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.
authors.affiliation: Ayse Basak Engin, Bensu Karahalil, Ali Esat Karakaya, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey.
authors.forename: Ayse Basak
authors.initials: AB
authors.lastname: Engin
authors.affiliation: Ayse Basak Engin, Bensu Karahalil, Ali Esat Karakaya, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey.
authors.forename: Bensu
authors.initials: B
authors.lastname: Karahalil
authors.affiliation: Ayse Basak Engin, Bensu Karahalil, Ali Esat Karakaya, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey.
authors.forename: Ali Esat
authors.initials: AE
authors.lastname: Karakaya
authors.affiliation: Ayse Basak Engin, Bensu Karahalil, Ali Esat Karakaya, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Engin
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016481:Helicobacter Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011446:Prospective Studies; D014364:Tryptophan / Q000097:blood*; D019139:Tumor Escape
chemical_list: D000907:Antibodies, Bacterial; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan
keywords: Colorectal cancer; Helicobacter pylori; Immune tolerance; Kynurenine/tryptophan; Oxidative stress
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