Inflammation and gut barrier function-related genes and colorectal cancer risk in western European populations-Reference-Cited by-同舟云学术

Inflammation and gut barrier function-related genes and colorectal cancer risk in western European populations

Published:2024-03-05 Issue: Volume: Page:
ISSN:0267-8357
Container-title:Mutagenesis
language:en
Short-container-title:

Author:

Mandle Hannah B¹^ORCID,Jenab Mazda²,Gunter Marc J²³,Tjønneland Anne⁴⁵,Olsen Anja⁵⁶^ORCID,Dahm Christina C⁶,Zhang Jie⁶,Sugier Pierre-Emmanuel⁷⁸,Rothwell Joseph⁷^ORCID,Severi Gianluca⁷,Kaaks Rudolf⁹^ORCID,Katzke Verena A⁹,Schulze Matthias B¹⁰¹¹^ORCID,Masala Giovanna¹²^ORCID,Sieri Sabina¹³^ORCID,Panico Salvatore¹⁴,Sacerdote Carlotta¹⁵^ORCID,Bonet Catalina¹⁶¹⁷,Sánchez Maria-Jose¹⁸¹⁹²⁰²¹,Amiano Pilar²⁰²²,Huerta José María²⁰²³,Guevara Marcela²⁰²⁴²⁵^ORCID,Palmqvist Richard²⁶,Löwenmark Thyra²⁶,Perez-Cornago Aurora²⁷^ORCID,Weiderpass Elisabete²⁸,Heath Alicia K³,Cross Amanda J³^ORCID,Vineis Paolo²⁹³⁰^ORCID,Hughes David J³¹^ORCID,Fedirko Veronika¹³²^ORCID

Affiliation:

1. Department of Epidemiology, Emory Rollins School of Public Health , Atlanta, GA 30322 , USA

2. Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO) , 69372 Lyon , France

3. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London , London, SW7 2AZ , UK

4. Diet, Cancer and Health, Danish Cancer Society Research Center , 2100 Copenhagen , Denmark

5. Department of Public Health, University of Copenhagen , 1353 Copenhagen K , Denmark

6. Department of Public Health, Aarhus University , DK-8000 Aarhus C , Denmark

7. Université Paris-Saclay, UVSQ, Inserm ‘Exposome and Heredity’ team, CESP U1018 , 94807 Villejuif Cedex , France

8. Laboratoire de Mathématiques et de leurs Applications de Pau E2S UPPA, CNRS , 64013 Pau Cedex , France

9. Division of Cancer Epidemiology, German Cancer Research Center, DKFZ , 69120 Heidelberg , Germany

10. Department of Molecular Epidemiology, German Institute of Human Nutrition , Potsdam-Rehbruecke, 14469 Nuthetal , Germany

11. Institute of Nutritional Science, University of Potsdam , 14469 Nuthetal , Germany

12. Institute for Cancer Research, Prevention and Clinical Network (ISPRO) , 50139 Florence , Italy

13. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , 20133 Milan , Italy

14. Dipartimento Di Medicina Clinica E Chirurgia, Federico II University , 80131 Naples , Italy

15. Unit of Cancer Epidemiology, AOU Città della Salute e della Scienza University Hospital , 10126 Turin , Italy

16. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO) , L’Hospitalet de Llobregat, 0890x Barcelona , Spain

17. Bellvitge Biomedical Research Institute (IDIBELL) , L’Hospitalet de Llobregat, 0890x Barcelona , Spain

18. Escuela Andaluza de Salud Pública (EASP) , 18011 Granada , Spain

19. Instituto de Investigación Biosanitaria ibs. 18011 Granada , Spain

20. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) , 28029 Madrid , Spain

21. Department of Preventive Medicine and Public Health, University of Granada , 18071 Granada , Spain

22. Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, BioGipuzkoa Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group , 20014 Donostia – San Sebastian , Spain

23. Department of Epidemiology, Murcia Regional Health Council-IMIB , 30120, El Palmar, Murcia , Spain

24. Instituto de Salud Pública y Laboral de Navarra , 31003 Pamplona, Navarra , Spain

25. Navarra Institute for Health Research (IdiSNA) , 31008 Pamplona, Navarra , Spain

26. Department of Medical Biosciences, Umea University , 901 87 Umeå , Sweden

27. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford , Oxford OX3 7LF , UK

28. Office of the Director, International Agency for Research on Cancer , 69366 Lyon Cedex 07 , France

29. MRC Centre for Environment and Health, School of public Health, Imperial College London , London W2 1PG , UK

30. Italian Institute for Genomic Medicine (IIGM) , 10060 Candiolo TO, Italy

31. Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin , Dublin 4 , Ireland

32. Department of Epidemiology, University of Texas M. D. Anderson Cancer Center , 77030 Houston, TX , USA

Abstract

Abstract Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn’s disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set of participants (Ncases = 1001; Ncontrols = 667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted ≤ 0.05 among controls. Among SNPs associated with a gut permeability score, 24 SNPs were in genes related to LPS sensing and mucin synthesis. Nine out of 12 SNPs associated with CRP were in genes related to inflammation or Crohn’s disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted ≤ 0.04) and at the gene level (Punadjusted ≤ 0.01). TLR4 rs10759934 was associated with rectal cancer but not colon cancer. Similarly, IL10 was associated with rectal cancer risk at an SNP and gene level (both Punadjusted ≤ 0.01), but not colon cancer. Genes and SNPs were selected a priori; therefore, we present unadjusted P-values. However, no association was statistically significant after multiple testing correction. This large and comprehensive study has identified gut barrier function and inflammation-related genes possibly contributing to CRC risk in European populations and is consistent with potential etiological links between host genetic background, gut barrier permeability, microbial endotoxemia, and CRC development.

Funder

Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award

Health Research Board (HRB) of Ireland health research award

Wereld Kanker Onderzoek Fonds

World Cancer Research Fund (WCRF) International Regular Grant Programme

International Agency for Research on Cancer

Department of Epidemiology and Biostatistics

School of Public Health, Imperial College London

NIHR Imperial Biomedical Research Centre

Danish Cancer Society

Ligue Contre le Cancer

Institut Gustave Roussy