Department of Radiotherapy, The First Hospital of Putian City, Putian, Fujian 351100, China.
Department of Proctology of Traditional Chinese Medicine, The First Hospital of Putian City, Putian, Fujian 351100, China.
Aging (Albany NY). 2024 Jun 13;16(12):10366-10379. doi: 10.18632/aging.205934.
Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of these cancers, and circulating inflammatory proteins may play a role in their development. However, the causal relationship between specific plasma proteins and urological malignancies remains unclear.
We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS). Instrumental variables representing genetic variants associated with circulating inflammatory proteins were used to infer causality on the risk of kidney, bladder, and prostate cancer. Four MR methods were utilized to provide robust effect estimates.
Our analysis identified several plasma proteins associated with a lower risk of kidney and bladder cancer, including Eukaryotic translation initiation factor 4E-binding protein 1, Caspase 8, Natural killer cell receptor 2B4, and Tumor necrosis factor ligand superfamily member 12. However, after adjusting for multiple testing, these associations did not remain statistically significant. For prostate cancer, CUB domain-containing protein 1 and Interleukin-10 receptor subunit beta were found to be protective, while Glial cell line-derived neurotrophic factor and SIR2-like protein 2 were identified as risk factors. After FDR adjustment, none of the inflammatory proteins were found to be significantly associated with a lower risk of prostate cancer.
Our findings suggest that certain plasma proteins may be involved in the development of urological malignancies. Mendelian randomization provides a useful framework for investigating causal relationships between inflammatory proteins and urological cancers, offering potential insights into their underlying biology and therapeutic targets.
泌尿系统恶性肿瘤，包括肾癌、膀胱癌和前列腺癌，是全球范围内的主要健康关注点。炎症与这些癌症的发病机制有关，循环炎症蛋白可能在其发展中发挥作用。然而，特定血浆蛋白与泌尿系统恶性肿瘤之间的因果关系尚不清楚。
我们使用全基因组关联研究（GWAS）的汇总统计数据进行了两样本孟德尔随机化（MR）分析。代表与循环炎症蛋白相关的遗传变异的工具变量用于推断这些蛋白对肾癌、膀胱癌和前列腺癌风险的因果关系。使用了四种 MR 方法来提供稳健的效应估计值。
我们的分析确定了几种与肾癌和膀胱癌风险降低相关的血浆蛋白，包括真核起始因子 4E 结合蛋白 1、半胱氨酸蛋白酶 8、自然杀伤细胞受体 2B4 和肿瘤坏死因子配体超家族成员 12。然而，在进行多重检验调整后，这些关联不再具有统计学意义。对于前列腺癌，CUB 结构域蛋白 1 和白细胞介素-10 受体亚基β被发现具有保护作用，而胶质细胞源性神经营养因子和 SIR2 样蛋白 2 被鉴定为危险因素。在 FDR 调整后，没有一种炎症蛋白与前列腺癌风险降低显著相关。
我们的研究结果表明，某些血浆蛋白可能参与了泌尿系统恶性肿瘤的发展。孟德尔随机化为研究炎症蛋白与泌尿系统癌症之间的因果关系提供了一个有用的框架，为它们的潜在生物学和治疗靶点提供了潜在的见解。
