循环中的C-反应蛋白水平与肺癌风险之间的遗传相关性和因果关系
Jiajun Shi1, Wanqing Wen1, Jirong Long1
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37023, USA.
Cancer causes & control : CCC
|February 9, 2024
概括
遗传因素将C反应性蛋白 (CRP) 水平与肺癌 (LC) 风险联系起来. 循环中的CRP水平显示出与小细胞肺癌 (SCLC) 风险的潜在因果关系.
科学领域:
- 遗传学 遗传学 是一个
- 流行病学 流行病学
- 在瘤学瘤学.
背景情况:
- 循环C反应蛋白 (CRP) 是一种炎症标记物.
- 炎症与癌症的发展有关.
- 慢性肺炎和肺癌 (LC) 风险之间的遗传关系需要进一步阐明.
研究的目的:
- 调查循环CRP水平与LC风险之间的遗传相关性.
- 确定CRP水平和LC风险之间的因果关系,包括组织学亚型.
主要方法:
- 利用全基因组关联研究 (GWAS) 的总结统计数据,用于欧洲祖先的CRP水平 (n=575,531) 和LC风险 (n=29,266例,56,450对照).
- 使用链接不平衡得分 (LDSC) 回归来评估遗传相关性.
- 应用孟德尔随机化 (MR) 分析,包括基于最大概率的方法,以推断因果关系.
主要成果:
- LDSC回归显示了CRP水平与整体LC,肺状细胞癌 (SCC) 和小细胞肺癌 (SCLC) 风险之间的显著正遗传相关性 (r=0.12-0.26,FDR调整后p<0.05).
- 无变MR显示CRP与增加的SCC风险之间的名义关联,在调整吸烟和BMI时减弱.
- 限制最大概率MR确定了CRP水平与整体LC (OR=1.06),SCC (OR=1.06) 和SCLC (OR=1.09) 的显著因果关联.
- 在大多数MR分析中观察到CRP和SCLC风险之间的一致关联.
结论:
- 在循环CRP水平和SCLC风险之间存在潜在的遗传和因果关系.
- 这些发现与之前的观察性研究一致,表明炎症在SCLC病变发生过程中的作用.
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