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Epidemiology

Dietary intake of isoflavones and coumestrol and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

British Journal of Cancer volume 132, pages 266–275 (2025)Cite this article

Subjects

Abstract

Background

Although phytoestrogens modulated pancreatic tumour growth in experimental studies, it remains unclear whether phytoestrogen intake is associated with pancreatic cancer.

Methods

Of 92,278 persons who completed the Diet History Questionnaire in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 346 were diagnosed with pancreatic cancer within a median follow-up of 9.4 years. Cox proportional hazards regression was used to evaluate pancreatic cancer risk in relation to phytoestrogen intake.

Results

After adjustment for confounders, intakes of glycitein and formononetin were associated with a reduced risk of pancreatic cancer [highest vs. lowest quartile, hazard ratio (HR) (95% confidence interval (CI)) for glycitein: 0.60 (0.39, 0.92); P for linear trend: 0.01; HR for formononetin: 0.51 (0.37, 0.70); P for linear trend: 0.005]. These associations were stronger and their linear trends across the quartiles of intakes were more statistically significant among ever smokers than never-smokers. A reduced risk was also observed for ever smokers in the highest quartile of total isoflavones or daidzein compared with those in the lowest quartile.

Conclusions

Our study suggests that high intakes of total isoflavones and some individual isoflavones were inversely associated with pancreatic cancer risk, but this potential protective effect was confined to ever smokers.

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Data availability

PLCO data analysed in the present study will be provided upon request, pending approval from the National Cancer Institute. Data requests can be made via the Cancer Data Access System at https://cdas.cancer.gov/plco/.

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Acknowledgements

We are grateful to the National Cancer Institute for providing access to the data from the PLCO Cancer Screening Trial. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by the National Cancer Institute.

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Authors and Affiliations

  1. Department of Gastroenterology, The Second Hospital of Shanxi Medical University, Taiyuan, PR China

    Chunliang Liu

  2. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA

    Chunliang Liu & Jianjun Zhang

  3. Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA

    Michael Reger

  4. Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN, USA

    Hao Fan

  5. Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, PR China

    Jintao Wang

  6. Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA

    Jianjun Zhang

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Contributions

The authors’ responsibilities were as follows—C.L., M.R., H.F., J.W. and J.Z.: participated in the review and revision of the manuscript; C.L. and J.Z.: designed and conducted research; C.L.: analysed data; C.L. and J.Z.: wrote the paper; J.Z.: had primary responsibility for final content; All authors: read and approved the final manuscript.

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Correspondence to Jianjun Zhang.

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All methods were conducted in compliance with the relevant ethical guidelines and regulations. The PLCO Cancer Screening Trial was approved by both the institutional review boards of the National Cancer Institute and all participating screening centres

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Liu, C., Reger, M., Fan, H. et al. Dietary intake of isoflavones and coumestrol and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Br J Cancer 132, 266–275 (2025). https://doi.org/10.1038/s41416-024-02929-8

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