TY - JOUR
T1 - Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations
AU - Nimptsch, Katharina
AU - Aleksandrova, Krasimira
AU - Fedirko, Veronika
AU - Jenab, Mazda
AU - Gunter, Marc J
AU - Siersema, Peter D
AU - Wu, Kana
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - Panico, Salvatore
AU - Palli, Domenico
AU - May, Anne M
AU - Sieri, Sabina
AU - Bueno-de-Mesquita, Bas
AU - Standahl, Karina
AU - Sánchez, Maria-Jose
AU - Perez-Cornago, Aurora
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Bonet, Catalina Bonet
AU - Dahm, Christina C
AU - Chirlaque, María-Dolores
AU - Fiano, Valentina
AU - Tumino, Rosario
AU - Gurrea, Aurelio Barricarte
AU - Boutron-Ruault, Marie-Christine
AU - Menegaux, Florence
AU - Severi, Gianluca
AU - van Guelpen, Bethany
AU - Lee, Young-Ae
AU - Pischon, Tobias
N1 - Funding Information:
We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.
Funding Information:
The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI https://doi.org/10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research.
Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC).
Funding Information:
We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/6/24
Y1 - 2022/6/24
N2 - 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.
AB - 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.
KW - C-Reactive Protein/analysis
KW - Colorectal Neoplasms/diagnosis
KW - Genetic Predisposition to Disease
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Prospective Studies
KW - Risk Factors
UR - https://www.scopus.com/pages/publications/85132685809
U2 - 10.1186/s12885-022-09778-9
DO - 10.1186/s12885-022-09778-9
M3 - Article
C2 - 35739525
SN - 1471-2407
VL - 22
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 695
ER -