Risk factors for neuroendocrine neoplasms - protocol for a case–control study based on a record linkage of registry and claims data

Sep 23, 2026

Recent research indicates rising neuroendocrine neoplasms, particularly in the digestive tract, with proposed contributors including family cancer history, tobacco smoking, alcohol use, and metabolic disorders such as diabetes and obesity. Depressive disorders may represent an additional risk, either directly or through linked behaviours and/or antidepressant medication. This protocol describes a German case–control study designed to identify risk factors for neuroendocrine neoplasms using registry and claims data linkage.

LanguageEnglish

CategoryHealthcare

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Pages6

Reading Time15 min

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Abstract

Background

Methods and analysis

Ethics and dissemination

Strengths and limitations of this study

Background

Open access Protocol Risk factors for neuroendocrine neoplasms: protocol for a case–control study based on a record linkage of registry and claims data Sven Voigtländer ,1 Roman Gerlach,2 Nina Grundmann ,1 Ewan Donnachie,2 Ursula Berger ,3 Amir Hakimhashemi,1 Martin Meyer,1 Martin Tauscher,2 Jacqueline Müller-Nordhorn1 To cite: Voigtländer S, Gerlach R, Grundmann N, et al. Risk factors for neuroendocrine neoplasms: protocol for a case–control study based on a record linkage of registry and claims data. BMJ Open 2025;15:e096273 . doi:10 . 1136/ bmjopen-2024-096273 ► Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[bmjopen-2024-096273](bmjopen-2024-096273)) . Ewan Donnachie deceased on 7 October 2024. Received 07 November 2024 Accepted 30 April 2025 © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. 1Bavarian Cancer Registry, Bavarian Health and Food Safety Authority, Nuremberg, Germany 2Bavarian Association of Statutory Health Insurance Accredited Physicians, Munich, Germany 3Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-MaximiliansUniversität, Munich, Germany Correspondence to Dr Sven Voigtländer; [sven.voigtlaender@lgl.bayern.de](sven.voigtlaender@lgl.bayern.de) ABSTRACT Background Recent studies showed an increase inneuroendocrine neoplasms, especially for the digestive tract. Several risk factors have been suggested to explain this increase, including a family history of cancer, tobacco smoking, alcohol consumption and metabolic disorders such as diabetes and obesity. Another risk factor may be depressive disorders, which could increase the risk of neuroendocrine neoplasms either directly or mediated through associated risk behaviours and/or antidepressant medication. Here, we outline the design of our study to identify the risk factors for neuroendocrine neoplasms in Germany. Methods and analysis A case–control study of the resident population of Bavaria, the second most populous federal state in Germany, based on a record linkage of data from the Bavarian Cancer Registry and data from the Bavarian Association of Statutory Health Insurance Accredited Physicians. Cases have a diagnosis of a malignant neuroendocrine neoplasm, either of the bronchopulmonary system or the gastroenteropancreatic system, in the period from 2021 to 2023. Controls are sampled from the non-cases and matched on sex, birth year (in 5-year intervals) and time of diagnosis (by calendar quarter) . Risk factor prevalence of cases and controls is assessed on the basis of assured outpatient diagnoses, that is, diagnoses documented in at least 2 out of 4 consecutive quarters in the 16 quarters preceding the diagnosis of a neuroendocrine neoplasm. The analysis uses conditional logistic regression to estimate ORs and 95% CIs. Ethics and dissemination This study protocol was approved by the Ethics Committee of the Bavarian State Chamber of Physicians (reference number: 24008) . Approval by the supervisory authority has been obtained from the Bavarian State Ministry of Health, Care, and Prevention (reference number: G35h-A1080-2023/20-2) and also the Bavarian Data Protection Commissioner stated to have no concerns after presentation of the study protocol (reference number: DSB/7-692/1-275) . The results of the case–control study will be presented at national as well as international conferences and be published in the form of scientific articles in peer-reviewed journals. Trial registration number NCT06282016. STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ Cases and controls will be drawn from an unselected source population, that is, persons who were insured with the Statutory Health Insura

FAQs

What risk factors does the study protocol aim to investigate for neuroendocrine neoplasms in Germany?

The protocol focuses on risk factors suggested by recent literature, including family history of cancer, tobacco smoking, alcohol consumption, metabolic disorders like diabetes and obesity, and the potential role of depressive disorders.

How are cases and controls selected in the case–control design?

Cases are malignant neuroendocrine neoplasm diagnoses in Bavaria during 2021–2023, with controls sampled from non-cases and matched on sex, birth year in 5-year intervals, and time of diagnosis by calendar quarter.

How will exposure status (risk factor prevalence) be measured and analyzed?

Risk factor prevalence is based on assured outpatient diagnoses recorded at least 2 out of 4 consecutive quarters in the 16 quarters preceding diagnosis. Conditional logistic regression will estimate odds ratios (ORs) with 95% confidence intervals.

Sep 23, 2026

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