Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study.


Journal

Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 28 06 2023
accepted: 16 07 2023
medline: 30 10 2023
pubmed: 21 8 2023
entrez: 20 8 2023
Statut: ppublish

Résumé

Resistin, a novel pro-inflammatory protein implicated in inflammatory processes, has been suggested to play a role in colorectal development. However, evidence from observational studies has been inconsistent. Mendelian randomization may be a complementary method to examine this association. We conducted a two-sample Mendelian randomization to estimate the association between genetically determined circulating resistin concentrations and risk of colorectal cancer (CRC). Protein quantitative trait loci (pQTLs) from the SCALLOP consortium were used as instrumental variables (IVs) for resistin. CRC genetic summary data was obtained from GECCO/CORECT/CCFR (the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry), and FinnGen (Finland Biobank). The inverse variance weighted method (IVW) was applied in the main analysis, and other robust methods were used as sensitivity analyses. Estimates for the association from the two data sources were then pooled using a meta-analysis approach. Thirteen pQTLs were identified as IVs explaining together 7.80% of interindividual variation in circulating resistin concentrations. Based on MR analyses, genetically determined circulating resistin concentrations were not associated with incident CRC (pooled-IVW-OR per standard deviation of resistin, 1.01; 95% CI 0.96, 1.06; p = 0.67. Restricting the analyses to using IVs within or proximal to the resistin-encoding gene (cis-IVs), or to IVs located elsewhere in the genome (trans-IVs) provided similar results. The association was not altered when stratified by sex or CRC subsites. We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC.

Identifiants

pubmed: 37599317
doi: 10.1007/s00432-023-05193-0
pii: 10.1007/s00432-023-05193-0
pmc: PMC10602946
doi:

Substances chimiques

Resistin 0

Types de publication

Meta-Analysis Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

14889-14900

Informations de copyright

© 2023. The Author(s).

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Auteurs

Thu Thi Pham (TT)

Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.

Katharina Nimptsch (K)

Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.

Nikos Papadimitriou (N)

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, 69372, Lyon, Cedex 08, France.

Krasimira Aleksandrova (K)

Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359, Bremen, Germany.
Faculty of Human and Health Sciences, University of Bremen, 28359, Bremen, Germany.

Mazda Jenab (M)

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, 69372, Lyon, Cedex 08, France.

Marc J Gunter (MJ)

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, 69372, Lyon, Cedex 08, France.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Loic Le Marchand (L)

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.

Li Li (L)

Department of Family Medicine and UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia, USA.

Brigid M Lynch (BM)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.

Sergi Castellví-Bel (S)

Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Amanda I Phipps (AI)

Fred Hutchinson Cancer Center, Seattle, WA, USA.

Stephanie L Schmit (SL)

Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Shuji Ogino (S)

Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.

Edward Giovannucci (E)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Tobias Pischon (T)

Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany. tobias.pischon@mdc-berlin.de.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany. tobias.pischon@mdc-berlin.de.
Biobank Technology Platform, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany. tobias.pischon@mdc-berlin.de.
Core Facility Biobank, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 13125, Berlin, Germany. tobias.pischon@mdc-berlin.de.

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