Getu Mikiyas Amare, Zhang Xianbin, Ying Ying, Gong Peng
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China.
Department of General Surgery, Institute of Precision Diagnosis and Treatment of Digestive System Tumors and Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, Guangdong, China.
Sci Rep. 2025 Apr 3;15(1):11371. doi: 10.1038/s41598-025-89288-3.
Previous observational studies have suggested a potential link between Type 1 Diabetes (T1D) and site-specific cancer risk. However, the nature of this association remains uncertain due to confounding factors, reverse causation, and biases inherent in observational research. To address this gap, we conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between T1D and 22 site-specific cancers. Using summary statistics from large-scale genome-wide association studies of European ancestry, comprising data on T1D (N = 520,580) and the 22 site-specific cancers, we selected single nucleotide polymorphisms strongly associated with T1D as instruments for our analysis. Causal relationships were primarily evaluated through inverse-variance weighting-based analyses, supplemented by three additional methods: MR-Egger, weighted median, and mode-based estimate. Sensitivity analyses were performed, excluding genetic variants with potential pleiotropic effects. The finding demonstrated a causal association between T1D and increased risks of lung cancer (OR = 1.018, 95% CI 1.004-1.033, p = 0.011), colorectal cancer (OR = 1.022, 95% CI 1.003-1.041, p = 0.019), and prostate cancer (OR = 1.018, 95% CI 1.005-1.030, p = 0.006). Conversely, T1D was associated with decreased risks of breast cancer (OR = 0.989, 95% CI 0.981-0.998, p = 0.016), lymphoma (OR = 0.999, 95% CI 0.974-0.999, p = 0.003), malignant melanoma (OR = 0.999, 95% CI 0.989-0.999, p = 0.001), and non-melanoma skin cancer (OR = 0.999, 95% CI 0.899-0.999, p = 0.003). Our MR study provides an evidence of causal association between T1D and altered risks of various site-specific cancers. Further research is recommended to validate this finding in diverse populations to enhance the generalizability of findings across different ethnic groups.
以往的观察性研究表明1型糖尿病（T1D）与特定部位癌症风险之间可能存在联系。然而，由于混杂因素、反向因果关系以及观察性研究中固有的偏差，这种关联的性质仍不确定。为了填补这一空白，我们进行了一项两样本孟德尔随机化（MR）研究，以评估T1D与22种特定部位癌症之间的因果关系。利用欧洲血统大规模全基因组关联研究的汇总统计数据，包括T1D（N = 520,580）和22种特定部位癌症的数据，我们选择了与T1D强烈相关的单核苷酸多态性作为分析工具。因果关系主要通过基于逆方差加权的分析进行评估，并辅以另外三种方法：MR-Egger、加权中位数和基于模式的估计。进行了敏感性分析，排除了具有潜在多效性影响的基因变异。研究结果表明，T1D与肺癌风险增加（OR = 1.018，95% CI 1.004 - 1.033，p = 0.011）、结直肠癌风险增加（OR = 1.022，95% CI 1.003 - 1.041，p = 0.019）和前列腺癌风险增加（OR = 1.018，95% CI 1.005 - 1.030，p = 0.006）之间存在因果关联。相反，T1D与乳腺癌风险降低（OR = 0.989，95% CI 0.981 - 0.998，p = 0.016）、淋巴瘤风险降低（OR = 0.999，95% CI 0.974 - 0.999，p = 0.003）、恶性黑色素瘤风险降低（OR = 0.999，95% CI 0.989 - 0.999，p = 0.001）和非黑色素瘤皮肤癌风险降低（OR = 0.999，95% CI 0.899 - 0.999，p = 0.003）相关。我们的MR研究提供了T1D与各种特定部位癌症风险改变之间因果关联的证据。建议进一步开展研究，在不同人群中验证这一发现，以提高研究结果在不同种族群体中的普遍性。
