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Associations between pregnancy-related factors and birth characteristics with risk of rare uterine cancer subtypes: a Nordic population-based case–control study

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Abstract

Purpose

Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas.

Methods

This nested case–control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined.

Results

Having a very-low-birth-weight infant (< 1500 vs. 2500–3999 g: OR [95% CI] 2.83 [1.61–4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20–2.23]) and type 1 endometrial carcinomas (0.35 [0.30–0.41]) but not uterine sarcomas (1.33 [0.90–1.98], p-heterogeneity < 0.01).

Conclusion

Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.

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Data availability

The datasets analyzed as part of the current study are not publicly available due to national regulations.

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Funding

This work was supported by the following: Nordic Cancer Union; Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation; Danish Cancer Society; Swedish Cancer Society (CAN 2016/440); and the intramural research program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Dr. Trabert received support from the Huntsman Cancer Institute/Huntsman Cancer Foundation.

Author information

Authors and Affiliations

  1. School of Medicine, University of Utah, Salt Lake City, UT, USA

    Jazmine Abril

  2. Department of Obstetrics and Gynecology, Huntsman Cancer Institute at the University of Utah, University of Utah, 2000 Circle of Hope Dr. Research South #4719, Salt Lake City, UT, 84112, USA

    Britton Trabert

  3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Rebecca Troisi

  4. Cancer Registry of Norway, Oslo, Norway

    Tom Grotmol, Steinar Tretli & Tone Bjørge

  5. Clinical Epidemiology Division, Department of Medicine, Karolinska Institute, Stockholm, Sweden

    Anders Ekbom & Ingrid Glimelius

  6. Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway

    Anders Engeland

  7. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway

    Anders Engeland & Tone Bjørge

  8. Department of Knowledge Brokers, THL Finnish Institute for Health and Welfare, Helsinki, Finland

    Mika Gissler

  9. Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden

    Mika Gissler

  10. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

    Mika Gissler

  11. Department of Immunology, Genetics and Pathology, Cancer Precision Medicine, Uppsala University, Uppsala, Sweden

    Ingrid Glimelius

  12. Finnish Cancer Registry, Helsinki, Finland

    Laura Madanat-Harjuoja

  13. Department of Pediatrics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Laura Madanat-Harjuoja

  14. Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark

    Anne Gulbech Ording & Henrik Toft Sørensen

Authors
  1. Jazmine Abril
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  2. Britton Trabert
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  3. Rebecca Troisi
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  4. Tom Grotmol
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  5. Anders Ekbom
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  6. Anders Engeland
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  7. Mika Gissler
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  9. Laura Madanat-Harjuoja
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  11. Henrik Toft Sørensen
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  12. Steinar Tretli
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  13. Tone Bjørge
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Contributions

The first draft of the manuscript was written by JA. All authors contributed to study conceptualization, editing, revising, and critical review of the analytic results. Data curation was led by TB and TG. Material preparation and analyses were performed by BT. BT takes responsibility for the content of the manuscript. RT, TG, AE, AE, MG, IG, LMH, AGO, HTS, ST, TB, and BT participated in the working group that developed numerous projects to evaluate pregnancy factors and female cancer risk in the Nordic countries database. All authors commented on previous versions of the manuscript and read and approved the final manuscript.

Corresponding author

Correspondence to Britton Trabert.

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Competing interest

The authors declare no competing interests.

Ethical approval

We obtained approval for this study from Ethics Committees in Norway and Sweden, from the Data Protection Agency in Denmark, and from the Finnish Institute for Health and Welfare in Finland after consulting its Data Protection Authority.

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Abril, J., Trabert, B., Troisi, R. et al. Associations between pregnancy-related factors and birth characteristics with risk of rare uterine cancer subtypes: a Nordic population-based case–control study. Cancer Causes Control 35, 741–747 (2024). https://doi.org/10.1007/s10552-023-01832-6

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  • DOI: https://doi.org/10.1007/s10552-023-01832-6

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