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Peptic ulcer as mediator of the association between risk of gastric cancer and socioeconomic status, tobacco smoking, alcohol drinking and salt intake
  1. Giulia Collatuzzo1,
  2. Gianfranco Alicandro2,3,
  3. Paola Bertuccio4,5,
  4. Claudio Pelucchi4,
  5. Rossella Bonzi4,
  6. Domenico Palli6,
  7. Monica Ferraroni4,
  8. Weimin Ye7,
  9. Amelie Plymoth7,
  10. David Zaridze8,
  11. Dmitry Maximovich8,
  12. Nuria Aragones9,10,
  13. Gemma Castaño-Vinyals9,11,12,13,
  14. Jesus Vioque9,14,
  15. Manoli Garcia de la Hera9,14,
  16. Zuo-Feng Zhang15,
  17. Jinfu Hu16,
  18. Lizbeth Lopez-Carrillo17,
  19. Malaquías López-Cervantes18,
  20. Michela Dalmartello4,
  21. Lina Mu19,
  22. Mary H Ward20,
  23. Charles Rabkin20,
  24. Guo-Pei Yu21,
  25. M Constanza Camargo20,
  26. Maria Paula Curado22,
  27. Nuno Lunet23,24,25,
  28. Eva Negri1,4,
  29. Carlo La Vecchia4,
  30. Paolo Boffetta1,26
  1. 1 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
  2. 2 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
  3. 3 Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  4. 4 Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, Università degli Studi di Milano, Milan, Italy
  5. 5 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
  6. 6 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy
  7. 7 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  8. 8 Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia
  9. 9 Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
  10. 10 Cancer Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain
  11. 11 Barcelona Institute for Global Health—ISGlobal, Barcelona, Spain
  12. 12 IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
  13. 13 Universitat Pompeu Fabra (UPF), Barcelona, Spain
  14. 14 Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernandez (ISABIAL-UMH), Alicante, Spain
  15. 15 Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
  16. 16 Harbin Medical University, Harbin, People's Republic of China
  17. 17 Mexico National Institute of Public Health, Morelos, Mexico
  18. 18 Facultad de Medicina, UNAM. Coyoacán, Mexico
  19. 19 Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
  20. 20 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
  21. 21 Medical Informatics Center, Peking University, Peking, People's Republic of China
  22. 22 Centro Internacional de Pesquisa, A. C. Camargo Cancer Center, São Paulo, Brazil
  23. 23 EPIUnit – Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal
  24. 24 Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal
  25. 25 Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
  26. 26 Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA
  1. Correspondence to Paolo Boffetta, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; paolo.boffetta{at}


Background Peptic ulcer disease (PUD) and gastric cancer (GC) are more prevalent in individuals with low socioeconomic status (SES) and share several risk factors. The aim of this study was to investigate the mediating role of PUD in the association between established risk factors and GC.

Methods We conducted a pooled analysis of 12 studies from the Stomach Cancer Pooling Project Consortium, including a total of 4877 GC cases and 11 808 controls. We explored the mediating role of PUD in the association between SES, tobacco smoking, heavy alcohol drinking and salt intake, and GC. Also, we assessed the ORs and 95% CIs of the risk factors and both PUD and GC.

Results PUD mediated 36% of the smoking effect mainly among men. Other risk factors were only slightly mediated by PUD (SES, 5.3%; heavy alcohol drinking, 3.3%; and salt intake, 2.5%). No significant difference was found when excluding PUD diagnosed within 2 years from GC.

Conclusions Our study provides innovative information on the mechanism of stomach mucosal damage leading to PUD and GC, with respect to the effect of tobacco smoking in particular.

  • Gastric cancer
  • Peptic ulcer disease
  • Mediation analysis
  • Smoking
  • Socioeconomic status
  • Alcohol
  • Salt

Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author upon reasonable request and approval by members of StoP Project Consortium.

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Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author upon reasonable request and approval by members of StoP Project Consortium.

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  • Contributors Conception and design of study: GC, GA, PBe, EN and PBo; acquisition of data: DP, MF, WY, AP, DZ, DM, NA, GC-V, JV, MGdlH, Z-FZ, JH, LL-C, ML-C, MD, LM, MHW, CR, G-PY, MCC, MPC, NL, EN and CLV; management, analysis and interpretation of data: GC, GA, PBe, CP, RB and PBo; drafting the manuscript: GC and PBo; critical revision of the manuscript for important intellectual content: GA, PBe, CP, EN and CLV; approval of final manuscript: all authors. Guarantor: PBo.

  • Funding This study was funded by the Associazione Italiana per la Ricerca sul Cancro (project number 21378, investigator grant). The authors thank the European Cancer Prevention Organization for providing support for the project meetings.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.