BMC Cancer (Jun 2022)

Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

  • Katharina Nimptsch,
  • Krasimira Aleksandrova,
  • Veronika Fedirko,
  • Mazda Jenab,
  • Marc J. Gunter,
  • Peter D. Siersema,
  • Kana Wu,
  • Verena Katzke,
  • Rudolf Kaaks,
  • Salvatore Panico,
  • Domenico Palli,
  • Anne M May,
  • Sabina Sieri,
  • Bas Bueno-de-Mesquita,
  • Karina Standahl,
  • Maria-Jose Sánchez,
  • Aurora Perez-Cornago,
  • Anja Olsen,
  • Anne Tjønneland,
  • Catalina Bonet Bonet,
  • Christina C. Dahm,
  • María-Dolores Chirlaque,
  • Valentina Fiano,
  • Rosario Tumino,
  • Aurelio Barricarte Gurrea,
  • Marie-Christine Boutron-Ruault,
  • Florence Menegaux,
  • Gianluca Severi,
  • Bethany van Guelpen,
  • Young-Ae Lee,
  • Tobias Pischon

DOI
https://doi.org/10.1186/s12885-022-09778-9
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 13

Abstract

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Abstract 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.