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:10.1186/s12885-022-09778-9

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 BonetChristina 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

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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.

Original language	English
Article number	695
Journal	BMC Cancer
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s12885-022-09778-9
Publication status	Published - 24 Jun 2022

Keywords

C-Reactive Protein/analysis
Colorectal Neoplasms/diagnosis
Genetic Predisposition to Disease
Humans
Polymorphism, Single Nucleotide
Prospective Studies
Risk Factors

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Nimptsch, K., Aleksandrova, K., Fedirko, V., Jenab, M., Gunter, M. J., Siersema, P. D., Wu, K., Katzke, V., Kaaks, R., Panico, S., Palli, D., May, A. M., Sieri, S., Bueno-de-Mesquita, B., Standahl, K., Sánchez, M.-J., Perez-Cornago, A., Olsen, A., Tjønneland, A., ... Pischon, T. (2022). Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations. BMC Cancer, 22(1), Article 695. https://doi.org/10.1186/s12885-022-09778-9

@article{22c4d044a587428dbfe3cc19d1755e3d,

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

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.",

keywords = "C-Reactive Protein/analysis, Colorectal Neoplasms/diagnosis, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors",

author = "Katharina Nimptsch and Krasimira Aleksandrova and Veronika Fedirko and Mazda Jenab and Gunter, {Marc J} and Siersema, {Peter D} and Kana Wu and Verena Katzke and Rudolf Kaaks and Salvatore Panico and Domenico Palli and May, {Anne M} and Sabina Sieri and Bas Bueno-de-Mesquita and Karina Standahl and Maria-Jose S{\'a}nchez and Aurora Perez-Cornago and Anja Olsen and Anne Tj{\o}nneland and Bonet, {Catalina Bonet} and Dahm, {Christina C} and Mar{\'i}a-Dolores Chirlaque and Valentina Fiano and Rosario Tumino and Gurrea, {Aurelio Barricarte} and Marie-Christine Boutron-Ruault and Florence Menegaux and Gianluca Severi and {van Guelpen}, Bethany and Young-Ae Lee and Tobias Pischon",

note = "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 G{\'e}n{\'e}rale de l{\textquoteright}Education Nationale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (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 Andaluc{\'i}a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Sk{\aa}ne and V{\"a}sterbotten (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: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jun,

day = "24",

doi = "10.1186/s12885-022-09778-9",

language = "English",

volume = "22",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central",

number = "1",

}

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, M-J, Perez-Cornago, A, Olsen, A, Tjønneland, A, Bonet, CB, Dahm, CC, Chirlaque, M-D, Fiano, V, Tumino, R, Gurrea, AB, Boutron-Ruault, M-C, Menegaux, F, Severi, G, van Guelpen, B, Lee, Y-A & Pischon, T 2022, 'Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations', BMC Cancer, vol. 22, no. 1, 695. https://doi.org/10.1186/s12885-022-09778-9

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 - http://www.scopus.com/inward/record.url?scp=85132685809&partnerID=8YFLogxK

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 -

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

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