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

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.