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

Journal of Cancer Research and Clinical Oncology · 16 authors, 25 centres

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TL;DR

It found no statistically significant association between genetically determined resistin concentrations and the risk of colorectal cancer.

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Genetic data were sourced from the GECCO/CORECT/CCFR consortium and FinnGen. The primary inverse variance weighted (IVW) meta-analysis yielded a pooled odds ratio of 1.01 (95% CI 0.96, 1.06; p=0.67) per standard deviation increase in resistin. Sensitivity analyses using MR-Egger, weighted median, and other methods, as well as analyses restricted to cis- or trans-pQTLs, showed no significant associations. Subgroup analyses by sex and CRC subsites also indicated no significant relationships. The study concludes there is no evidence linking genetically predicted resistin levels to CRC risk.

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other

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epidemiology

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ORIGINAL PAPER

PMC10602946

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

Journal of Cancer Research and Clinical Oncology

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ABSTRACT

Abstract Purpose 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. Methods 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. Results 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. Conclusions We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-023-05193-0. Keywords: Resistin, Colorectal cancer, Mendelian randomization, Genetic, Instrumental

CITATION EXPORT

Thu Thi Pham, Katharina Nimptsch, Nikos Papadimitriou et al.. Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study. Journal of Cancer Research and Clinical Oncology. (2023). https://doi.org/10.1007/s00432-023-05193-0

AUTHORS

16 · 25 CENTRES

Thu Thi Pham, Katharina Nimptsch, Nikos Papadimitriou, Krasimira Aleksandrova, Mazda Jenab, Marc J Gunter, Loic Le Marchand, Li Li, Brigid M Lynch, Sergi Castellví-Bel, Amanda I Phipps, Stephanie L Schmit, Hermann Brenner, Shuji Ogino, Edward Giovannucci, Tobias Pischon

1Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
2Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
3Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, 69372 Lyon, Cedex 08, France
4Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, 28359 Bremen, Germany
5Faculty of Human and Health Sciences, University of Bremen, 28359 Bremen, Germany
6Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
7Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813 USA
8Department of Family Medicine and UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia USA
9Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia
10Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
11Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
12Department 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
13Fred Hutchinson Cancer Center, Seattle, WA USA
14Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH USA
15Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH USA
16Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
17Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
18German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
19Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA USA
20Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA USA
21Broad Institute of MIT and Harvard, Cambridge, MA USA
22Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA USA
23Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA USA
24Biobank Technology Platform, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
25Core Facility Biobank, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany

Thu Thi Pham, Katharina Nimptsch, Nikos Papadimitriou et al.. Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study. Journal of Cancer Research and Clinical Oncology. (2023). https://doi.org/10.1007/s00432-023-05193-0