PDF(Pubmed)
Abstract：
BACKGROUND: Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear.
METHODS: Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results.
RESULTS: Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1_20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2_0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships.
CONCLUSIONS: Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application.
METHODS: Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results.
RESULTS: Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1_20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2_0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships.
CONCLUSIONS: Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application.
摘要：
背景：消化系统癌症代表了重大的全球健康挑战，并归因于人口统计学和生活方式变化的结合。脂质组学已成为癌症研究的关键领域，提示脂质代谢的改变与癌症的发展密切相关。然而,特定血脂谱与消化系统癌症风险之间的因果关系尚不清楚.
方法：使用双样本孟德尔随机化（MR）方法，我们阐明了脂质体谱与五种消化系统癌症风险之间的因果关系：胃，肝脏,食道,胰腺,和大肠癌。这项研究的目的是利用来自GWAS目录和英国生物银行等公共数据库的数据，研究发展脂质分布对消化系统癌症风险的影响。使用逆方差加权（IVW）方法和其他严格的MR方法来评估潜在的因果关系。此外,我们进行了敏感性分析和反向MR分析,以确保结果的稳健性.
结果：在某些脂类性状与发生消化系统癌症的风险之间确定了显著的因果关系。鞘磷脂(d40:1)水平升高与胃癌发病风险降低相关(比值比(OR)=0.68,P<0.001),而磷脂酰胆碱水平升高(16:1_20:4)会增加患食管癌的风险(OR=1.31,P=0.02)。相反，磷脂酰胆碱(18:2_0:0)对大肠癌有保护作用(OR=0.86,P=0.036)。双向分析并未表明癌症风险与血脂水平之间存在反向因果关系。严格的MR方法证明了上述因果关系的稳健性。
结论：我们的发现强调了特定的脂质组学特征与发生各种消化系统癌症的风险之间的显着因果关系，强调脂质分布在癌症预防和治疗策略中的潜力。这些结果加强了MR在解开复杂的脂质-癌症相互作用中的价值，为研究和临床应用提供了新的途径。
方法：使用双样本孟德尔随机化（MR）方法，我们阐明了脂质体谱与五种消化系统癌症风险之间的因果关系：胃，肝脏,食道,胰腺,和大肠癌。这项研究的目的是利用来自GWAS目录和英国生物银行等公共数据库的数据，研究发展脂质分布对消化系统癌症风险的影响。使用逆方差加权（IVW）方法和其他严格的MR方法来评估潜在的因果关系。此外,我们进行了敏感性分析和反向MR分析,以确保结果的稳健性.
结果：在某些脂类性状与发生消化系统癌症的风险之间确定了显著的因果关系。鞘磷脂(d40:1)水平升高与胃癌发病风险降低相关(比值比(OR)=0.68,P<0.001),而磷脂酰胆碱水平升高(16:1_20:4)会增加患食管癌的风险(OR=1.31,P=0.02)。相反，磷脂酰胆碱(18:2_0:0)对大肠癌有保护作用(OR=0.86,P=0.036)。双向分析并未表明癌症风险与血脂水平之间存在反向因果关系。严格的MR方法证明了上述因果关系的稳健性。
结论：我们的发现强调了特定的脂质组学特征与发生各种消化系统癌症的风险之间的显着因果关系，强调脂质分布在癌症预防和治疗策略中的潜力。这些结果加强了MR在解开复杂的脂质-癌症相互作用中的价值，为研究和临床应用提供了新的途径。
