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Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study

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Abstract

Purpose

Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs.

Methods

We performed a retrospective case–control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors.

Results

Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31–3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39–4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18–2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08–0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05–5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08–5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28–5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11–3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38–4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08–3.33, p = 0.026).

Conclusion

This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.

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Availability of data and material

The datasets generated during end/or analyzed during the current study are available from the corresponding author on reasonable requests.

Code availability

Not applicable.

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Acknowledgements

We wish to thank the NETTARE Unit – NeuroEndocrine Tumor TAsk foRcE of “Sapienza” University of Rome, Italy, led by Prof. Andrea Lenzi, Prof. Andrea M. Isidori and Prof. Elisa Giannetta, for integrating the patient’s multidisciplinary clinical, diagnostic and therapeutic management and follow-up.

Funding

This study was partially supported by the ministerial research project PRIN2017Z3N3YC.

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Author notes

  1. T. Feola and G. Puliani contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy

    T. Feola, G. Puliani, F. Sesti, R. Centello, V. Di Vito, A. Lenzi, A. M. Isidori & E. Giannetta

  2. Neuroendocrinology, Neuromed Institute, IRCCS, Pozzilli, Italy

    T. Feola

  3. Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy

    G. Puliani, R. Lauretta & M. Appetecchia

  4. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

    R. Modica, R. Minotta, G. Cannavale, S. Di Meglio & A. Colao

  5. Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

    A. Faggiano

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  1. T. Feola
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  2. G. Puliani
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Corresponding author

Correspondence to E. Giannetta.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The study was approved by the local review board at Regina Elena National Cancer Institute of Rome (Reference number 1370/20).

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Informed consent was obtained from all individual participants included in the study.

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Feola, T., Puliani, G., Sesti, F. et al. Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study. J Endocrinol Invest 45, 849–857 (2022). https://doi.org/10.1007/s40618-021-01715-0

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