PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：泌尿系恶性肿瘤，包括肾脏,膀胱,前列腺癌，是全球主要的健康问题。炎症与这些癌症的发病机理有关，和循环炎症蛋白可能在它们的发育中起作用。然而,特定血浆蛋白与泌尿系恶性肿瘤之间的因果关系尚不清楚.
方法：我们使用全基因组关联研究（GWAS）的汇总统计进行了双样本孟德尔随机化（MR）分析。代表与循环炎症蛋白相关的遗传变异的仪器变量用于推断肾脏风险的因果关系。膀胱,和前列腺癌。利用四种MR方法来提供稳健的效果估计。
结果：我们的分析确定了几种与肾癌和膀胱癌风险较低相关的血浆蛋白，包括真核翻译起始因子4E结合蛋白1、Caspase8、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,在调整多次测试后，这些关联没有统计学意义.对于前列腺癌，含有CUB结构域的蛋白1和白细胞介素-10受体亚基β被发现具有保护性，而胶质细胞源性神经营养因子和SIR2样蛋白2被确定为危险因素。FDR调整后，没有发现炎性蛋白与较低的前列腺癌风险显著相关.
结论：我们的研究结果表明，某些血浆蛋白可能参与泌尿系恶性肿瘤的发展。孟德尔随机化为研究炎症蛋白和泌尿系癌症之间的因果关系提供了一个有用的框架。提供对其潜在生物学和治疗目标的潜在见解。
方法：我们使用全基因组关联研究（GWAS）的汇总统计进行了双样本孟德尔随机化（MR）分析。代表与循环炎症蛋白相关的遗传变异的仪器变量用于推断肾脏风险的因果关系。膀胱,和前列腺癌。利用四种MR方法来提供稳健的效果估计。
结果：我们的分析确定了几种与肾癌和膀胱癌风险较低相关的血浆蛋白，包括真核翻译起始因子4E结合蛋白1、Caspase8、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,在调整多次测试后，这些关联没有统计学意义.对于前列腺癌，含有CUB结构域的蛋白1和白细胞介素-10受体亚基β被发现具有保护性，而胶质细胞源性神经营养因子和SIR2样蛋白2被确定为危险因素。FDR调整后，没有发现炎性蛋白与较低的前列腺癌风险显著相关.
结论：我们的研究结果表明，某些血浆蛋白可能参与泌尿系恶性肿瘤的发展。孟德尔随机化为研究炎症蛋白和泌尿系癌症之间的因果关系提供了一个有用的框架。提供对其潜在生物学和治疗目标的潜在见解。
