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Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project

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Abstract

Background

Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium.

Methods

A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis.

Results

A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58–0.96). Compared with never use, ever, 5–9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58–0.92), 0.53 (95% CI: 0.34–0.84) and 0.71 (95% CI: 0.50–1.00), respectively. The associations were generally similar for anatomical and histologic subtypes.

Conclusion

Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.

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Data availability

The data underlying this article are subject to restrictions, as they were used under license for this study and so are not publicly available. However, they will be shared on reasonable request to the authors and after permission of the Steering Committee of the StoP Project.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

DHEA:

Dehydroepiandrosterone

FFQs:

Food frequency questionnaires

HR:

Hazard ratio

MHT:

Menopausal hormone therapy

OR:

Odds ratio

StoP Project:

Stomach cancer Pooling Project

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Acknowledgements

The authors thank the European Cancer Prevention Organization for providing support for the project meetings.

Funding

The StoP Project was funded by the AIRC (Associazione Italiana per la Ricerca sul Cancro) Foundation (Project number 21378, Investigator Grant), the Italian Ministry of Health (Grant RF-2021-12373951) and the Italian Ministry of University and Research (PRIN 2022, Grant 2022A4WZFC). This study was partially funded by the Intramural Program of the National Cancer Institute, United States.

Author information

Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

    Minkyo Song, Charles S. Rabkin, Linda M. Liao, Mary H. Ward, Rashmi Sinha & M. Constanza Camargo

  2. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia

    Harindra Jayasekara

  3. School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia

    Harindra Jayasekara

  4. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia

    Harindra Jayasekara

  5. Branch of Medical Statistics, Biometry, and Epidemiology “G. A. Maccacaro”, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Claudio Pelucchi, Monica Ferraroni, Rossella Bonzi & Carlo La Vecchia

  6. School of Epidemiology and Public Health, Department of Medicine, University of Ottawa, Ottawa, ON, Canada

    Kenneth C. Johnson

  7. Harbin Medical University, Harbin, China

    Jinfu Hu

  8. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy

    Domenico Palli

  9. Department of Clinical Epidemiology, N.N. Blokhin National Medical Research Center for Oncology, Moscow, Russia

    David Zaridze & Dmitry Maximovitch

  10. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain

    Nuria Aragonés, Vicente Martin, Gemma Castaño-Vinyals, Marcela Guevara & Jesus Vioque

  11. Cancer Registration and Surveillance Unit, Public Health Division, Department of Health of Madrid, Madrid, Spain

    Nuria Aragonés

  12. Instituto de Biomedicina (IBIOMED), Universidad de León, León, Spain

    Vicente Martin

  13. Barcelona Institute for Global Health—ISGlobal, Barcelona, Spain

    Gemma Castaño-Vinyals

  14. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    Gemma Castaño-Vinyals

  15. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Gemma Castaño-Vinyals

  16. Instituto de Salud Pública y Laboral de Navarra, 31003, Pamplona, Spain

    Marcela Guevara

  17. Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain

    Marcela Guevara

  18. Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan

    Shoichiro Tsugane & Akihisa Hidaka

  19. National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan

    Shoichiro Tsugane

  20. Nikkei Disease Prevention Center, São Paulo, Brazil

    Gerson Shigueaki Hamada

  21. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

    Eva Negri & Paolo Boffetta

  22. Department of Public and Community Health, School of Public Health, University of West Attica, Athens, Greece

    Areti Lagiou

  23. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Pagona Lagiou

  24. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Pagona Lagiou

  25. Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA

    Paolo Boffetta

  26. Centro Internacional de Pesquisa, A. C. Camargo Cancer Center, São Paulo, Brazil

    Maria Paula Curado

  27. EPIUnit – Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal

    Nuno Lunet

  28. Laboratório Para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal

    Nuno Lunet

  29. Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal

    Nuno Lunet

  30. Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernandez (ISABIAL-UMH), Alicante, Spain

    Jesus Vioque

  31. Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

    Zuo-Feng Zhang

Authors
  1. Minkyo Song
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  2. Harindra Jayasekara
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  3. Claudio Pelucchi
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  4. Charles S. Rabkin
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  6. Jinfu Hu
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  7. Domenico Palli
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  8. Monica Ferraroni
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  9. Linda M. Liao
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  10. Rossella Bonzi
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  11. David Zaridze
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  13. Nuria Aragonés
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  14. Vicente Martin
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  15. Gemma Castaño-Vinyals
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  16. Marcela Guevara
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  29. Zuo-Feng Zhang
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  30. Carlo La Vecchia
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  31. M. Constanza Camargo
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Contributions

MS and MCC led study conceptualization and design. CSR, KCJ, JH, DP, MF, LML, RB, DZ, DM, NA, VM, GC-V, MG, ST, GSH, AH, EN, MHW, RS, AL, PL, and CLV collected the original data and provided them to StoP. CP, RB and EN, members of the StoP coordinating center harmonized core variables and contributed to database management. MS harmonized the data on reproductive factors and performed the statistical analysis. MS and HJ drafted the manuscript. All authors contributed to data interpretation and critical revision of the manuscript for important intellectual content. All authors read and approved the final version of the manuscript. MCC was responsible for study supervision.

Corresponding author

Correspondence to M. Constanza Camargo.

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Supplementary Information

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10552_2023_1829_MOESM1_ESM.pdf

Supplementary file1 (PDF 24 KB)— Sensitivity analysis assessing associations between selected reproductive factors and overall gastric cancer in the Stomach cancer Pooling (StoP) Project based on using pooled individual-level data. Study-specific models adjusted for age, smoking, alcohol use, vegetable intake, salt intake, family history of gastric cancer, and socioeconomic status. OR, odds ratio, 95% CI, confidence interval, MHT menopausal hormone therapy

Supplementary file2 (DOCX 38 KB)

10552_2023_1829_MOESM3_ESM.pdf

Supplementary file3 (PDF 17 KB)—Associations between age at first full-term pregnancy and corresponding interval from menarche and overall gastric cancer risk among parous women in the Stomach cancer Pooling (StoP) Project. Study-specific models adjusted for age, smoking, drinking, vegetable intake, salt intake, family history of gastric cancer, and socioeconomic status. OR, odds ratio, 95% CI, confidence interval, menopausal hormone therapy

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Song, M., Jayasekara, H., Pelucchi, C. et al. Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project. Cancer Causes Control 35, 727–737 (2024). https://doi.org/10.1007/s10552-023-01829-1

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