Annals of Hematology

, Volume 98, Issue 8, pp 1981–1987 | Cite as

Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan

  • Naoyo Ishikura
  • Yoshiaki Usui
  • Hidemi Ito
  • Yumiko Kasugai
  • Isao Oze
  • Seiichi Kato
  • Yasushi Yatabe
  • Shigeo Nakamura
  • Keitaro MatsuoEmail author
Original Article


Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45–1.33), 0.65 (0.30–1.39), 1.03 (0.38–2.79), and 0.84 (0.22–3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30–3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00–3.86), 1.92 (0.74–4.95), and 5.80 (1.12–30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.


Helicobacter pylori Gastric lymphoma MALT lymphoma Atrophic gastritis Case-control study 



We thank the doctors, nurses, and technical and administration staff of Aichi Cancer Center for their daily administration of the HERPACC study.

Funding information

Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, consisting of Priority Areas of Cancer (No. 17015018), Innovative Areas (No. 221S0001), and JSPS KAKENHI Grant (26860430, 16H06277, and 15 K08792) and a Grant-in-Aid for the Third Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures performed in this study involving human participants have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards of the institutional Ethics Committee and with the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.

Supplementary material

277_2019_3721_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 14 kb)
277_2019_3721_MOESM2_ESM.docx (15 kb)
ESM 2 (DOCX 14 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Division of Cancer Epidemiology and PreventionAichi Cancer Center Research InstituteNagoyaJapan
  3. 3.Division of Cancer Information and ControlAichi Cancer Center Research InstituteNagoyaJapan
  4. 4.Department of EpidemiologyNagoya University Graduate School of MedicineNagoyaJapan
  5. 5.Department of Pathology and Molecular DiagnosticsAichi Cancer Center HospitalNagoyaJapan

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