Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study

Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Kana Wu, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, Joseph Rothwell, Rudolf Kaaks, Verena Katzke, Alberto Catalano, Claudia Agnoli, Giovanna Masala, Maria Santucci De Magistris, Rosario Tumino, Roel Vermeulen, Amaia Aizpurua, Camino Trobajo-SanmartínMaría-Dolores Chirlaque, Maria-Jose Sánchez, Sai San Moon Lu, Amanda J Cross, Sofia Christakoudi, Elisabete Weiderpass, Tobias Pischon

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HR Q4vsQ1  = 0.95, 95% CI: 0.73-1.23; P trend  = .97; and HR per doubling of resistin concentration  = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Original languageEnglish
Pages (from-to)1596-1606
Number of pages11
JournalInternational Journal of Cancer
Volume154
Issue number9
Early online date10 Jan 2024
DOIs
Publication statusPublished - 1 May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Funding

V. Fedirko is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar of Cancer Research and is supported by the CPRIT Rising Stars Award (Grant ID RR200056). The authors thank all participants in the EPIC study for their outstanding cooperation. We acknowledge the use of data and biological samples from the following EPIC sub-cohorts: EPIC-Denmark Aarhus Centre, PI Kim Overvad; EPIC-Germany Postdam, PI. Matthias Schulze; EPIC – The Netherlands – Bilthoven center, PI. Monique Verschuren; EPIC-Spain Asturias center, PI Ramón Quirós; EPIC-UK Norfolk center, PI Nick Wareham; EPIC-UK Oxford center, PI. Tim Key. We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. Open Access funding enabled and organized by Projekt DEAL. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and 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). The national cohorts are supported by the 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); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); the Italian Association for Research on Cancer (AIRC) and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), the World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands); ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).

FundersFunder number
CPRIT Rising Stars AwardRR200056
Dutch Prevention Funds
Dutch ZON (Zorg Onderzoek Nederland
ISCIII RETICRD06/0020
LK Research Funds
NKR
National Institute for Public Health and the Environment
Netherlands Cancer Registry
Nordic Centre of Excellence programme on Food, Nutrition and Health
Cancer Prevention and Research Institute of Texas
Kræftens Bekæmpelse
Deutsches Krebsforschungszentrum
Centre International de Recherche sur le Cancer
University of Maryland School of Public Health
Department of Epidemiology and Biostatistics, University of California, San Francisco
Medical Research Council
Cancer Research UK
World Cancer Research FundERC‐2009‐AdG 232997
Imperial College London
Institut national de la santé et de la recherche médicale
Bundesministerium für Bildung und Forschung
Cancerfonden
Ministerie van Volksgezondheid, Welzijn en Sport
Ligue Contre le Cancer
Vetenskapsrådet
Consiglio Nazionale delle Ricerche
Instituto de Salud Carlos III
NordForsk
Associazione Italiana per la Ricerca sul Cancro
Deutsche Krebshilfe
Rijksinstituut voor Volksgezondheid en Milieu
Institut Gustave-Roussy
Mutuelle Générale de l'Education Nationale
Consejería de Salud y Familias, Junta de Andalucía
NIHR Imperial Biomedical Research Centre
Hellenic Health Foundation

    Keywords

    • EPIC
    • colorectal cancer
    • mortality
    • pre-diagnostic
    • resistin
    • survival

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