Li Xujia, Huang Lingli, Yan Yue, Rong Yuming, Chen Xuxian, Gao Mengge, Huang Jinsheng
VIP Department, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
Discov Oncol. 2025 May 21;16(1):841. doi: 10.1007/s12672-025-02678-x.
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.
A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms.
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.
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.
及时识别可改变的风险因素在肿瘤预防中至关重要。我们旨在仔细研究一系列基因可改变的风险因素与五种不同神经内分泌肿瘤之间的因果关系。
采用双向双样本孟德尔随机化（MR）分析来阐明41种潜在风险因素与五种神经内分泌肿瘤之间的因果关系。
身高、1级、2级和3级肥胖、超重、腰臀比、腰围和血清尿酸被确定为与结直肠神经内分泌肿瘤风险增加相关的因素（所有p<0.05）。相反，空腹血糖与结直肠神经内分泌肿瘤风险之间呈负相关（p=0.031）。血小板计数与肺神经内分泌肿瘤呈负相关（p=0.02）。此外，腰臀比与胰腺神经内分泌肿瘤风险呈负相关。心房颤动、平均红细胞血红蛋白含量和平均红细胞体积与小肠神经内分泌肿瘤风险呈正相关。在胃神经内分泌肿瘤中，1级和2级肥胖、超重和端粒长度与风险增加有关。在进行多次检验校正后，1级肥胖对结直肠神经内分泌肿瘤仍具有统计学意义，端粒长度与胃神经内分泌肿瘤的关联仍具有显著性。反向MR结果提示端粒长度与胃神经内分泌肿瘤之间存在双向因果关系。
本研究为潜在可改变风险因素与五种神经内分泌肿瘤风险之间的因果关系提供了遗传学证据。针对这些因素的治疗方法可能为预防神经内分泌肿瘤提供依据。
