血清C反应蛋白和遗传风险在恶性肿瘤发病中的联合作用

朱梦怡; 汪天培; 颜财旺; 朱猛; 靳光付

doi:10.16462/j.cnki.zhjbkz.2021.09.004

血清C反应蛋白和遗传风险在恶性肿瘤发病中的联合作用

doi: 10.16462/j.cnki.zhjbkz.2021.09.004

211166 南京，南京医科大学公共卫生学院流行病学系

基金项目:

国家自然科学基金 81872702

国家自然科学基金 82003534

江苏省自然科学基金 BK20200674

详细信息

通讯作者:
靳光付, E-mail: guangfujin@njmu.edu.cn

中图分类号: R181.2;R73-31
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- 被引次数: 0
出版历程
- 收稿日期: 2021-08-13
- 修回日期: 2021-08-24
- 网络出版日期: 2021-10-23
- 刊出日期: 2021-09-10

Joint effect of serum C-reactive protein and genetic risk in the pathogenesis of cancer

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China

Funds:

National Natural Science Foundation of China 81872702

National Natural Science Foundation of China 82003534

National Natural Science Foundation of Jiangsu Province BK20200674

More Information

Corresponding author: JIN Guang-fu, E-mail: guangfujin@njmu.edu.cn

摘要

摘要: 目的探讨血清C反应蛋白(C-reactive protein, CRP)和遗传风险在恶性肿瘤发病中的联合作用。方法基于英国生物样本库(UK Biobank, UKB)以及前期已构建的全恶性肿瘤多基因遗传风险评分(cancer polygenic risk score, CPRS)，将研究对象分为高、中、低三个遗传风险组，同时按照血清CRP浓度的自然对数值大小将研究对象分为高、中、低三个水平组。采用Cox比例风险模型，分析不同遗传风险组中，血清CRP水平与恶性肿瘤发病风险的关联。结果共纳入420 940位研究对象，包括男性192 942名(45.84%)，女性227 998名(54.16%)。血清CRP水平与多种恶性肿瘤的发病风险均存在统计学关联，随着血清CRP水平的升高，男性和女性整体恶性肿瘤的发病风险均增加(男性：HR=1.09, 95% CI: 1.07~1.11; 女性：HR=1.09, 95% CI: 1.07~1.11)；在低遗传风险组中，高水平CRP与恶性肿瘤发病风险关联效应更强(男性：HR=1.38；女性：HR=1.46)；在高遗传风险组中，高水平CRP与恶性肿瘤发病风险关联效应较弱(男性：HR=1.07；女性：HR=1.17)，呈负向交互作用。结论高血清CRP水平可增加恶性肿瘤发病风险，其在低遗传风险人群中可能具有更强的效应。
- 恶性肿瘤 /
- C反应蛋白 /
- 多基因风险评分 /
- 交互作用
Abstract: Objective To explore the joint effect of serum C-reactive protein (CRP) and genetic risk in the pathogenesis of cancer. Methods Based on UK Biobank data and the cancer polygenic risk score (CPRS) constructed previously, subjects were assigned into low, intermediate, and high genetic risk groups according to CPRS and were assigned into low, intermediate, and high groups based on natural logarithm of CRP. Cox proportional hazard model was used to test the association between serum CRP level and the risk of cancer in different genetic risk groups. Results A total of 420 940 subjects including 192 942 (45.84%) men and 227 998 (54.16%) women were included. The level of serum CRP was statistically associated with the risk of multiple cancers. High level of serum CRP was associated with an increased risk of overall cancer in male and female (male: HR=1.09, 95% CI: 1.07-1.11; female: HR=1.09, 95% CI: 1.07-1.11). The effect size of CRP on cancer risk was stronger in low genetic risk group (male: HR=1.38; female: HR=1.46) compared to that of high genetic risk group (male: HR=1.07; female: HR=1.17). There was a negative interaction between CRP and genetic risk in cancer. Conclusions High level of serum CRP can increase the cancer risk. Serum CRP level may have a stronger effect in low genetic risk population.
- Cancer /
- C-reactive protein /
- Polygenic risk score /
- Interaction

HTML全文

图 1 血清CRP水平的分布及其对恶性肿瘤发病风险的影响

Figure 1. The distribution of CRP level in serum and the effect on the risk of cancer

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图 2 血清CRP水平与各恶性肿瘤以及整体恶性肿瘤发病风险在不同性别人群中的关联

Figure 2. The associations between CRP level in serum and the risk of site-specific cancer and overall cancer by sex

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图 3 血清CRP水平与遗传风险对恶性肿瘤发病风险的联合效应

Figure 3. Joint effect of CRP level in serum and genetic risk on the risk of cancer by sex

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表 1 血清CRP水平与恶性肿瘤发病风险的关联(按遗传风险分层)

Table 1. The association between CRP level in serum and the risk of overall cancer (stratified by genetic risk)

性别	低遗传风险			中遗传风险			高遗传风险
性别	低CRP	中CRP	高CRP	低CRP	中CRP	高CRP	低CRP	中CRP	高CRP
男性
病例/人年	286/55 241	1 130/159 995	481/51 188	1 135/162 261	4 313/477 270	1 888/156 914	618/53 614	2 134/155 942	817/52 460
HR(95% CI)值	1.00	1.17(1.02~1.34)	1.38(1.18~1.61)	1.00	1.10(1.03~1.17)	1.33(1.23~1.43)	1.00	1.02(0.93~1.12)	1.07(0.96~1.20)
P值		0.020	＜0.001		0.006	＜0.001		0.680	0.208
女性
病例/人年	287/63 680	1 202/191 477	513/62 787	1 124/194 155	4 265/567 778	1747/187 793	520/63 985	1 874/185 814	736/63 371
HR(95% CI)值	1.00	1.19(1.04~1.36)	1.46(1.24~1.71)	1.00	1.10(1.03~1.18)	1.27(1.17~1.38)	1.00	1.08(0.98~1.20)	1.17(1.03~1.33)
P值		0.010	＜0.001		0.005	＜0.001		0.136	0.015

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