Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study

Abstract Background  The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms. Methods A bidirectional two-sam...

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Main Authors: Xujia Li, Lingli Huang, Yue Yan, Yuming Rong, Xuxian Chen, Mengge Gao, Jinsheng Huang
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02678-x
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author Xujia Li
Lingli Huang
Yue Yan
Yuming Rong
Xuxian Chen
Mengge Gao
Jinsheng Huang
author_facet Xujia Li
Lingli Huang
Yue Yan
Yuming Rong
Xuxian Chen
Mengge Gao
Jinsheng Huang
author_sort Xujia Li
collection DOAJ
description Abstract Background  The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms. Methods A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms. Results Height, obesity class 1, 2, and 3, overweight, waist-to-hip ratio, waist circumference, and serum uric acid were identified as factors associated with an augmented risk of colorectal neuroendocrine neoplasms (all p < 0.05). Conversely, a negative correlation was observed between fasting glucose and the risk of colorectal neuroendocrine neoplasms (p = 0.031). Platelet count exhibited a negative correlation with lung neuroendocrine neoplasms (p = 0.02). Moreover, the waist-to-hip ratio demonstrated a negative association with the risk of pancreatic neuroendocrine neoplasms. Atrial fibrillation, mean cell heamoglobin, and mean cell volume were positively associated with the risk of small intestine neuroendocrine neoplasms. In gastric neuroendocrine neoplasms, obesity class 1 and 2, overweight, and telomere length were implicated in their heightened risk. Following adjustment for multiple tests, obesity class 1 remained statistically significant to colorectal neuroendocrine neoplasms, and telomere length maintained significance in association with gastric neuroendocrine neoplasms. The outcomes of reverse MR suggested a bidirectional causal relationship between telomere length and gastric neuroendocrine neoplasms. Conclusion This study provided genetic evidence for the causal relationships between potentially modifiable risk factors and the risk of five neuroendocrine neoplasms. Therapeutic approaches to these factors may provide a basis for preventing neuroendocrine neoplasms.
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spelling doaj-art-91a1e2970e4247fe9a9f9b49007fa35a2025-08-20T02:34:07ZengSpringerDiscover Oncology2730-60112025-05-0116111710.1007/s12672-025-02678-xAssociation of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization studyXujia Li0Lingli Huang1Yue Yan2Yuming Rong3Xuxian Chen4Mengge Gao5Jinsheng Huang6VIP Department, Sun Yat-Sen University Cancer CenterDepartment of Oncology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South UniversityState Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer CenterVIP Department, Sun Yat-Sen University Cancer CenterVIP Department, Sun Yat-Sen University Cancer CenterDepartment of Clinical Nutrition, Huadu District People’s HospitalVIP Department, Sun Yat-Sen University Cancer CenterAbstract Background  The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms. Methods A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms. Results Height, obesity class 1, 2, and 3, overweight, waist-to-hip ratio, waist circumference, and serum uric acid were identified as factors associated with an augmented risk of colorectal neuroendocrine neoplasms (all p < 0.05). Conversely, a negative correlation was observed between fasting glucose and the risk of colorectal neuroendocrine neoplasms (p = 0.031). Platelet count exhibited a negative correlation with lung neuroendocrine neoplasms (p = 0.02). Moreover, the waist-to-hip ratio demonstrated a negative association with the risk of pancreatic neuroendocrine neoplasms. Atrial fibrillation, mean cell heamoglobin, and mean cell volume were positively associated with the risk of small intestine neuroendocrine neoplasms. In gastric neuroendocrine neoplasms, obesity class 1 and 2, overweight, and telomere length were implicated in their heightened risk. Following adjustment for multiple tests, obesity class 1 remained statistically significant to colorectal neuroendocrine neoplasms, and telomere length maintained significance in association with gastric neuroendocrine neoplasms. The outcomes of reverse MR suggested a bidirectional causal relationship between telomere length and gastric neuroendocrine neoplasms. Conclusion This study provided genetic evidence for the causal relationships between potentially modifiable risk factors and the risk of five neuroendocrine neoplasms. Therapeutic approaches to these factors may provide a basis for preventing neuroendocrine neoplasms.https://doi.org/10.1007/s12672-025-02678-xModifiable risk factorsNeuroendocrine neoplasmsBidirectionalMendelian randomizationLifestyle factor
spellingShingle Xujia Li
Lingli Huang
Yue Yan
Yuming Rong
Xuxian Chen
Mengge Gao
Jinsheng Huang
Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
Discover Oncology
Modifiable risk factors
Neuroendocrine neoplasms
Bidirectional
Mendelian randomization
Lifestyle factor
title Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
title_full Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
title_fullStr Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
title_full_unstemmed Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
title_short Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study
title_sort association of modifiable risk factors and telomere length with five neuroendocrine neoplasms a bidirectional mendelian randomization study
topic Modifiable risk factors
Neuroendocrine neoplasms
Bidirectional
Mendelian randomization
Lifestyle factor
url https://doi.org/10.1007/s12672-025-02678-x
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