AUTHOR=Li Zhenqi , Jin Liquan , Xia Lu , Li Xiangzhi , Guan Yunfei , He Hongyang TITLE=Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1042567 DOI=10.3389/fonc.2023.1042567 ISSN=2234-943X ABSTRACT=Aim

To 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.

Methods

Based 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.

Results

BMI 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%.

Conclusions

In 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.