Your browser doesn't support javascript.
loading
A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.
Nounu, Aayah; Greenhough, Alexander; Heesom, Kate J; Richmond, Rebecca C; Zheng, Jie; Weinstein, Stephanie J; Albanes, Demetrius; Baron, John A; Hopper, John L; Figueiredo, Jane C; Newcomb, Polly A; Lindor, Noralane M; Casey, Graham; Platz, Elizabeth A; Le Marchand, Loïc; Ulrich, Cornelia M; Li, Christopher I; van Duijnhoven, Fränzel J B; Gsur, Andrea; Campbell, Peter T; Moreno, Víctor; Vodicka, Pavel; Vodickova, Ludmila; Brenner, Hermann; Chang-Claude, Jenny; Hoffmeister, Michael; Sakoda, Lori C; Slattery, Martha L; Schoen, Robert E; Gunter, Marc J; Castellví-Bel, Sergi; Kim, Hyeong Rok; Kweon, Sun-Seog; Chan, Andrew T; Li, Li; Zheng, Wei; Bishop, D Timothy; Buchanan, Daniel D; Giles, Graham G; Gruber, Stephen B; Rennert, Gad; Stadler, Zsofia K; Harrison, Tabitha A; Lin, Yi; Keku, Temitope O; Woods, Michael O; Schafmayer, Clemens; Van Guelpen, Bethany; Gallinger, Steven; Hampel, Heather.
Afiliação
  • Nounu A; Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom. an0435@bristol.ac.uk.
  • Greenhough A; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
  • Heesom KJ; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
  • Richmond RC; Centre for Research in Biosciences, The Faculty of Health and Applied Sciences, The University of the West of England, Bristol, United Kingdom.
  • Zheng J; Proteomics Facility, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom.
  • Weinstein SJ; Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Albanes D; Medical Research Council (MRC) Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Baron JA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Hopper JL; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Figueiredo JC; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
  • Newcomb PA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Lindor NM; Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
  • Casey G; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Platz EA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Le Marchand L; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Ulrich CM; School of Public Health, University of Washington, Seattle, Washington.
  • Li CI; Department of Health Science Research, Mayo Clinic, Scottsdale, Arizona.
  • van Duijnhoven FJB; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • Gsur A; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  • Campbell PT; University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Moreno V; Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.
  • Vodicka P; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Vodickova L; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
  • Brenner H; Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
  • Chang-Claude J; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Hoffmeister M; Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Sakoda LC; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
  • Slattery ML; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
  • Schoen RE; ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Gunter MJ; Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
  • Castellví-Bel S; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Kim HR; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
  • Kweon SS; Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
  • Chan AT; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Li L; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
  • Zheng W; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bishop DT; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Buchanan DD; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Giles GG; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gruber SB; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Rennert G; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Stadler ZK; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Harrison TA; Division of Research, Kaiser Permanente Northern California, Oakland, California.
  • Lin Y; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
  • Keku TO; Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Woods MO; Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Schafmayer C; Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
  • Van Guelpen B; Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
  • Gallinger S; Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
  • Hampel H; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea.
Artigo em Inglês | MEDLINE | ID: mdl-33318029
ABSTRACT

BACKGROUND:

Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.

METHODS:

Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).

RESULTS:

Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR 1.08, 95% CI, 1.03-1.13; OR 3.33, 95% CI, 2.46-4.50; and OR 1.15, 95% CI, 1.02-1.29, respectively).

CONCLUSIONS:

MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. IMPACT Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo observacional Idioma: Inglês Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Reino Unido

Similares

MEDLINE

...
LILACS

LIS

Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo observacional Idioma: Inglês Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Reino Unido