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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 May;92(5):488–493. doi: 10.1111/j.1349-7006.2001.tb01120.x

Low Expression Myeloperoxidase Genotype Negatively Associated with Helicobacter pylori Infection

Nobuyuki Hamajima 1,, Keitaro Matsuo 1,4, Takashi Suzuki 2, Tsuneya Nakamura 2, Akira Matsuura 2, Kazuo Tajima 1, Suketami Tominaga 3
PMCID: PMC5926737  PMID: 11376556

Abstract

Our previous study revealed that a polymorphism of the interleukin (IL) 1B gene, encoding the pro‐inflammatory cytokine IL‐lβ, influenced the prevalence of persistent Helicobacter pylori (HP) infection. In this paper, a polymorphism of another inflammation‐related enzyme, myeloperoxidase (MPO), was examined with respect to association with the HP infection. The polymorphism is due to a G‐to‐A transition at ‐463 in the promoter region of MPO. The G allele is the wild type with normal expression, while the A allele is a low expression allele. The subjects were 241 non‐cancer outpatients (118 males and 123 females) aged 39 to 69 who participated in an HP eradication program at Aichi Cancer Center Hospital. High‐molecular weight Campylobacter‐Associated‐Protein (HM‐CAP) ELISA (Enteric Products Ins., Westbury, NY) was used for the identification of HP‐infected participants. The frequency was 79.7% (192/241) for the GG genotype, 19.5% (47/241) for the GA genotype, and 0.8% (2/241) for the AA genotype. The sex‐age‐adjusted odds ratio (OR) relative to GG was 0.69 (95% confidence interval (CI), 0.35–1.35) for individuals with the A allele, but among male participants the OR was 0.31 (0.11–0.84). Subgroup analysis revealed significantly reduced ORs with the GA/AA genotypes for current smokers (0.19, 0.04–0.96), and for those who were occasional/no milk drinkers (0.25, 0.09–0.72). These findings are consistent with the results for IL‐1B in our earlier study, suggesting that inflammatory responses in the gastric mucosa may influence persistent HP infection, and that smoking and milk intake may be effect ‐modifiers.

Keywords: Helicobacter pylori infection, Myeloperoxidase, Lifestyle factors

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Reference

  • 1.Labenz , J. and Borsch , G . Evidence for the essential role of Helicobacter pylori in gastric ulcer disease . Gut , 35 , 19 – 22 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Kuippers , E. J. , Uyterlinde , A. M. , Pena , A. S. , Roosendaal , R. , Pals , G. , Nelis , G. F. , Festen , H. P. M. and Meuwissen , S. G. M . Long‐term sequelae of Helicobacter pylori gastritis . Lancet , 345 , 1525 – 1528 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 3.Munoz , N . Is Helicobacter pylori a cause of gastric cancer? An appraisal of the seroepidemiological evidence . Cancer Epidemiol. Biomarkers Prev. , 3 , 445 – 451 ( 1994. ). [PubMed] [Google Scholar]
  • 4.Dunn , B. E. , Cohen , H. and Blaser , M. J . Helicobacter pylori . Clin. Microbiol. Rev. , 10 , 720 – 741 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Banatvala , N. , Mayo , K. , Megraud , F. , Jennings , R. , Deeks , J. J. and Feldman , R. A . The cohort effect and Helicobacter pylori . J. Infect. Dis. , 168 , 219 – 221 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 6.Goodman , K. J. and Correa , P . The transmission of Helicobacter pylori. A critical review of the evidence . Int. J. Epidemiol. , 24 , 875 – 887 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 7.Cave , D. R . How is Helicobacter pylori transmitted ? Gastroenterology , 113 , S9 – S14 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 8.Tsugane , S. , Tei , Y. , Takahashi , T. , Watanabe , T. and Sugano , K . Salty food intake and risk of Helicobacter pylori infection . Jpn. J. Cancer Res. , 85 , 474 – 478 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Fontham , E. T. H. , Ruiz , B. , Perez , A. , Hunter , F. and Correa , P . Determinations of Helicobacter pylori infection and chronic gastritis . Am. J. Gastroenterol. , 90 , 1094 – 1101 ( 1995. ). [PubMed] [Google Scholar]
  • 10.Murray , L. J. , McCrum , E. E. , Evans , A. E. and Bamford , K. B . Epidemiology of Helicobacter pylori infection among 4742 randomly selected subjects from Northern Ireland . Int. J. Epidemiol. , 26 , 880 – 887 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 11.Woodward , M. , Morrison , C. and McColl , K . An investigation into factors associated with Helicobacter pylori infection . J. Clin. Epidemiol. , 53 , 175 – 182 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 12.Hamajima , N. , Inoue , M. , Tajima , K. , Tominaga , S. , Matsuura , A. , Kobayashi , S. and Ariyoshi , Y . Lifestyle and anti‐Helicobacter pylori immunoglobulin G antibody among outpatients . Jpn. J. Cancer Res. , 88 , 1038 – 1043 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Namekata , T. , Miki , K. , Kimmey , M. , Fritsche , T. , Hughes , D. , Moore , D. and Suzuki , K . Chronic atrophic gastritis and Helicobacter pylori infection among Japanese Americans in Seattle . Am. J. Epidemiol. , 151 , 820 – 830 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 14.The EUROGAST Study Group . Epidemiology of, and risk factors for Helicobacter pylori infection among 2194 asymptomatic subjects in 17 populations . Gut , 34 , 1672 – 1676 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Hamajima , N. , Matsuo , K. , Saito , T. , Tajima , K. , Okuma , K. , Yamao , K. and Tominaga , S . Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection . Jpn. J. Cancer Res. , 92 , 383 – 389 ( 2001. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Dianarello , C. A . Biologic basis for interleukin‐1 in disease . Blood , 87 , 2095 – 2147 ( 1996. ). [PubMed] [Google Scholar]
  • 17.Jung , H. , Kim , J. M. , Song , I. S. and Kim , C. Y . Helicobacter pylori induces an array of pro‐inflammatory cyto‐kines in human gastric epithelial cells: quantification of mRNA for interleukin‐8, ‐1 alpha/beta, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1 and tumor necrosis factor‐alpha . J. Gastroenterol. Hepatol , 12 , 473 – 480 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 18.Beales , I. L. and Calam , J . Interleukin 1 beta and tumour necrosis factor alpha inhibit acid secretion in cultured rabbit parietal cells by multiple pathways . Gut , 42 , 227 – 234 ( 1998. ). 9536948 [Google Scholar]
  • 19.Foster , C. B. , Lehrnbecher , T. , Mol , F. , Steinberg , S. M. , Venzon , D. J. , Walsh , T. J. , Noack , D. , Rae , J. , Winkelstein , J. A. , Curnutte , J. T. and Chanock , S. J . Host defense molecule polymorphisms influence the risk for immune‐mediated complications in chronic granulomatous disease . J. Clin. Invest. , 102 , 2146 – 2155 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Takemura , T. , Granger , D. N. , Evans , D. J. , Jr. , Evans , D. G. , Graham , D. Y. , Anderson , D. C. , Wolf , R. E. , Cepinskas , G. and Kvietys , P. R . Extract of Helicobacter pylori induces neutrophils to injure endothelial cells and contains antielastase activity . Gastroenterology , 110 , 21 – 29 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 21.Kim , J. S. , Jung , H. C. , Kim , J. M. , Song , I. S. and Kim , C. Y . Helicobacter pylori water‐soluble surface proteins activate human neutrophils and up‐regulate expression of CXC chemokines . Dig. Dis. Sci. , 45 , 83 – 92 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 22.Nauseef , W. M. , Brigham , S. and Cogley , M . Hereditary myeloperoxidase deficiency due to a missense mutation of arginine 569 to tryptophan . J. Biol. Chem. , 269 , 1212 – 1216 ( 1994. ). [PubMed] [Google Scholar]
  • 23.Piedrafita , F. J. , Molander , R. B. , Vansant , G. , Orlova , E. A. , Pfahl , M. and Reynolds , W. F . An Alu element in the myeloperoxidase promoter contains a composite SPl‐thyroid hormone‐retinoic acid response element . J. Biol. Chem. , 271 , 14412 – 14420 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 24.Cascorbi , L , Henning , S. , Brockmoller , J. , Gephart , J. , Meisel , C. , Muller , J. M. , Loddenkemper , R. and Roots , I . Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant ‐463 of the myeloperoxidase gene . Cancer Res. , 60 , 644 – 649 ( 2000. ). [PubMed] [Google Scholar]
  • 25.London , S. J. , Lehman , T. A. and Taylor , J. A . Myeloperoxidase genetic polymorphism and lung cancer risk . Cancer Res. , 57 , 5001 – 5003 ( 1997. ). [PubMed] [Google Scholar]
  • 26.Marchand , L. L. , Seifried , A. , Lum , A. and Wilkes , L. R . Association of the myeloperoxidase ‐463G→A polymorphism with lung cancer risk . Cancer Epidemiol. Biomarkers Prev. , 9 , 181 – 184 ( 2000. ). [PubMed] [Google Scholar]
  • 27.Schabath , M. B. , Spitz , M. R. , Zhang , X. , Delclos , G. L. and Wu , X . Genetic variations of myeloperoxidase and lung cancer risk . Carcinogenesis , 21 , 1163 – 1166 ( 2000. ). [PubMed] [Google Scholar]
  • 28.Matsuo , K. , Hamajima , N. , Shinoda , M. , Hatooka , S. , Inoue , M. , Takezaki , T. , Onda , H. and Tajima , K . Polymorphism of myeloperoxidase (MPO) and esophageal cancer risk . J. Epidemiol . ( 2001. ), in press . [DOI] [PubMed] [Google Scholar]
  • 29.Petruska , J. M. , Mosebrook , D. R. , Jakab , G. J. and Trush , M. A . Myeloperoxidase‐enhanced formation of (+‐)‐trans‐7,8‐dihydroxy‐7,8‐dihydrobenzo(a)pyrene‐DNA adducts in lung tissue in vitro: a role of pulmonary inflammation in the bioactivation of a procarcinogen . Carcinogenesis , 13 , 1075 – 1081 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 30.Evans , D. J. , Evans , D. G. , Graham , D. Y. and Klein , P. D.A sensitive and specific serologic test for detection of Campylobacter pylori infection . Gastroenterology , 96 , 1004 – 1008 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 31.Matsuo , K. , Hamajima , N. , Tominaga , S. , Suzuki , T. , Nakamura , T. , Matsuura , A. and Kitayama , K . Helicobacter pylori IgG antibody test established in the United States showed a substantial lower sensitivity for Japanese population . Am. J. Gastroenterol , 95 , 1597 – 1598 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 32.Carrington , M. , Dean , M. , Martin , M. P. and O'Brien , S. J . Genetics of HTV‐1 infection: chemokine receptor CCR5 polymorphism and its consequences . Hum. Mol. Genet. , 8 , 1939 – 1945 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 33.El‐Omar , E. M. , Carrington , M. , Chow , W.‐H. , McColl , K. E. L. , Bream , J. H. , Young , H. A. , Herrera , J. , Lissowska , J. , Yuan , C.‐C. , Rothman , N. , Lanyon , G. , Martin , M. , Fraumeni , J. F. , Jr. and Rabkin , C. S . Interleukin‐1 polymorphisms associated with increased risk of gastric cancer . Nature , 404 , 398 – 402 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 34.Bertoni , G. , Sassatelli , R. , Nigrisoli , E. , Tansini , P. , Bianchi , G. , Casa , G. D. , Gagni , A. and Bedogni , G . Triple therapy with azithromycin, omeprazole, and amoxicillin is highly effective in the eradication of Helicobacter pylori: a controlled trial versus omeprazole plus amoxicillin . Am. J. Gastroenterol , 91 , 258 – 263 ( 1996. ). [PubMed] [Google Scholar]
  • 35.Kamada , T. , Haruma , K. , Komoto , K. , Mihara , M. , Chen , X. , Yoshihara , M. , Sumii , K. , Kajiyama , G. , Tahara , K. and Kawamura , Y . Effect of smoking and histological gastritis severity on the rate of H. pylori eradication with omeprazole, amoxicillin, and clarithromycin . Helicobacter , 4 , 204 – 210 ( 1999. ). [DOI] [PubMed] [Google Scholar]

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