DataSheet_1_Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways.zip

AimTo explore whether C-reactive protein (CRP) mediates the risk of body mass index (BMI) in pancreatic cancer (PC) and calculate the mediate proportion of CRP in this possible mechanism.
MethodsBased on two-sample Mendelian randomization (TSMR), a two-step Mendelian randomization (TM) model was conducted to determine whether CRP was a mediator of the causal relationship between BMI and PC. The multivariable Mendelian randomization (MVMR) study was designed for mediating analysis and to calculate the mediating proportion mediated by CRP.
ResultsBMI has a positive causal relationship with PC (n = 393 SNPs, OR = 1.484, 95% CI: 1.021–2.157, p< 0.05). BMI has a positive causal relationship with CRP (n = 179 SNPs, OR = 1.393, 95% CI: 1.320–1.469, p< 0.05). CRP has a positive causal relationship with PC (n = 54 SNPs, OR = 1.348, 95% CI: 1.004–1.809, p< 0.05). After adjusting CRP, BMI has no causal relationship with PC (n = 334 SNPs, OR = 1.341, 95% CI: 0.884–2.037, p< 0.05). After adjusting BMI, there was still a positive causal relationship between CRP and PC (n = 334 SNPs, OR = 1.441, 95% CI: 1.064–1.950, p< 0.05). The mediating effect of CRP was 29%.
ConclusionsIn clinical practice, while actively advocating for weight loss among obese patients, we should focus on chronic inflammation levels in obese patients as well. In addition, anti-inflammatory dietary patterns and appropriate physical activity are important in preventing PC.

研究目的：本研究旨在探讨C反应蛋白（C-reactive protein, CRP）是否介导体重指数（body mass index, BMI）与胰腺癌（pancreatic cancer, PC）的发病风险关联，并计算CRP在该潜在致病机制中的介导比例。
方法：本研究基于双样本孟德尔随机化（two-sample Mendelian randomization, TSMR）设计，采用两步孟德尔随机化（two-step Mendelian randomization, TM）模型，以明确CRP是否为BMI与PC因果关联的中介因子；同时通过多变量孟德尔随机化（multivariable Mendelian randomization, MVMR）开展中介效应分析，并计算CRP所介导的效应占比。
结果：BMI与PC存在正向因果关联（纳入393个单核苷酸多态性位点（single nucleotide polymorphism, SNPs），比值比OR=1.484，95%置信区间CI：1.021~2.157，P<0.05）。BMI与CRP亦存在正向因果关联（纳入179个SNPs，OR=1.393，95%CI：1.320~1.469，P<0.05）。CRP与PC同样存在正向因果关联（纳入54个SNPs，OR=1.348，95%CI：1.004~1.809，P<0.05）。调整CRP水平后，BMI与PC的因果关联不再显著（纳入334个SNPs，OR=1.341，95%CI：0.884~2.037，P<0.05）。调整BMI水平后，CRP与PC仍存在正向因果关联（纳入334个SNPs，OR=1.441，95%CI：1.064~1.950，P<0.05）。CRP的中介效应占比为29%。
结论：临床实践中，在积极倡导肥胖患者减重的同时，亦应关注肥胖人群的慢性炎症状态。此外，抗炎饮食模式与适度体育运动在胰腺癌预防中具有重要价值。