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

Author:

Pham Thu Thi12ORCID,Nimptsch Katharina1ORCID,Aleksandrova Krasimira34,Jenab Mazda5,Fedirko Veronika67ORCID,Wu Kana8,Eriksen Anne Kirstine9,Tjønneland Anne910,Severi Gianluca11ORCID,Rothwell Joseph11,Kaaks Rudolf12,Katzke Verena12,Catalano Alberto13,Agnoli Claudia14,Masala Giovanna15,De Magistris Maria Santucci16,Tumino Rosario17,Vermeulen Roel18,Aizpurua Amaia1920,Trobajo‐Sanmartín Camino212223,Chirlaque María‐Dolores2224,Sánchez Maria‐Jose22252627,Lu Sai San Moon28,Cross Amanda J.29,Christakoudi Sofia2930ORCID,Weiderpass Elisabete31ORCID,Pischon Tobias123233ORCID

Affiliation:

1. Molecular Epidemiology Research Group Max‐Delbrueck‐Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany

2. Charité‐Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Hum‐boldt‐Universität zu Berlin Berlin Germany

3. Department of Epidemiological Methods and Etiological Research Leibniz Institute for Prevention Research and Epidemiology—BIPS Bremen Germany

4. Faculty of Human and Health Sciences University of Bremen Bremen Germany

5. Nutrition and Metabolism Branch International Agency for Research on Cancer (IARC‐WHO), World Health Organization Lyon France

6. Department of Epidemiology University of Texas M.D. Anderson Cancer Center Houston Texas USA

7. Department of Epidemiology, Rollins School of Public Health Emory University Atlanta Georgia USA

8. Department of Nutrition Harvard T.H. Chan School of Public Health Boston Massachusetts USA

9. Danish Cancer Society Research Center Copenhagen Denmark

10. Department of Public Health University of Copenhagen Copenhagen Denmark

11. Université Paris‐Saclay UVSQ, Inserm “Exposome and Heredity” Team Villejuif France

12. Department of Cancer Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany

13. Centre for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences University of Turin Orbassano Italy

14. Epidemiology and Prevention Unit, Department of Epidemiology and Data Science Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

15. Institute for Cancer Research Prevention and Clinical Network (ISPRO) Florence Italy

16. Azienda Ospedaliera Universitaria (AOU) Federico II Naples Italy

17. Hyblean Association for Epidemiological Research, AIRE ONLUS Ragusa Italy

18. Institute of Risk Assessment Sciences Utrecht University Utrecht The Netherlands

19. Ministry of Health of the Basque Government Sub Directorate for Public Health and Addictions of Gipuzkoa San Sebastian Spain

20. Biodonostia Health Research Institute Epidemiology of Chronic and Communicable Diseases Group San Sebastián Spain

21. Instituto de Salud Pública y Laboral de Navarra Pamplona Spain

22. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Madrid Spain

23. Navarre Institute for Health Research (IdiSNA) Pamplona Spain

24. Department of Epidemiology, Regional Health Council, IMIB‐Arrixaca Murcia University Murcia Spain

25. Escuela Andaluza de Salud Pública (EASP) Granada Spain

26. Instituto de Investigación Biosanitaria ibs.GRANADA Granada Spain

27. Department of Preventive Medicine and Public Health University of Granada Granada Spain

28. Department of Radiation Sciences, Oncology Unit Umeå University Umeå Sweden

29. Department of Epidemiology and Biostatistics, School of Public Health Imperial College London London UK

30. Department of Inflammation Biology, School of Immunology and Microbial Sciences King's College London London UK

31. International Agency for Research on Cancer World Health Organization Lyon France

32. Biobank Technology Platform Max‐Delbrueck‐Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany

33. Core Facility Biobank, Berlin Institute of Health Charité‐Universitätsmedizin Berlin Berlin Germany

Abstract

AbstractResistin 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 (HRQ4vsQ1 = 0.95, 95% CI: 0.73–1.23; Ptrend = .97; and HRper 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.

Funder

Centre International de Recherche sur le Cancer

Department of Epidemiology and Biostatistics, University of California, San Francisco

Kræftens Bekæmpelse

Ligue Contre le Cancer

Mutuelle Générale de l'Education Nationale

Institut National de la Santé et de la Recherche Médicale

Deutsche Krebshilfe

NordForsk

Cancer Research UK

Medical Research Council

Publisher

Wiley

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