Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations
Nimptsch K., Aleksandrova K., Fedirko V., Jenab M., Gunter MJ., Siersema PD., Wu K., Katzke V., Kaaks R., Panico S., Palli D., May AM., Sieri S., Bueno-de-Mesquita B., Standahl K., Sánchez MJ., Perez-Cornago A., Olsen A., Tjønneland A., Bonet CB., Dahm CC., Chirlaque MD., Fiano V., Tumino R., Gurrea AB., Boutron-Ruault MC., Menegaux F., Severi G., van Guelpen B., Lee YA., Pischon T.
Background: The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear. Methods: We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression. Results: During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively). Conclusions: The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.