Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses

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Seyed Khoei, NazlisadatDepartment of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria. (författare)

Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses

Artikel/kapitelEngelska2020

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2020-09-03
Springer Nature,2020
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-427542
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-427542URI
https://doi.org/10.1186/s12916-020-01703-wDOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-175926URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:144635887URI

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BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Anti-oxidants
Bilirubin
Cancer
Colorectal cancer
Mendelian randomization analysis

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Jenab, MazdaNutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.,Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. (författare)
Murphy, NeilNutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. (författare)
Banbury, Barbara L.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.,Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. (författare)
Carreras-Torres, RobertColorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat, Barcelona, Spain. (författare)
Viallon, VivianNutritional Methodology and Biostatistics Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69372, Lyon CEDEX 08, France. (författare)
Kühn, TilmanDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. (författare)
Bueno-de-Mesquita, BasDepartment for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands.; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. (författare)
Aleksandrova, KrasimiraGroup Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. (författare)
Cross, Amanda J.Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. (författare)
Weiderpass, ElisabeteInternational Agency for Research on Cancer (IARC-WHO), Lyon, France. (författare)
Stepien, MagdalenaNutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. (författare)
Bulmer, AndrewSchool of Medicine, Griffith University, Brisbane, QLD, Australia.; Alliance for Vascular Access Teaching and Research (AVATAR), Menzies Health Institute Queensland, Griffith University, Brisbane, QLD, Australia. (författare)
Tjønneland, AnneDanish Cancer Society Research Center, Copenhagen, Denmark.; Department of Public Health, University of Copenhagen, Copenhagen, Denmark. (författare)
Boutron-Ruault, Marie-ChristineCESP (Centre de Recherche en Epidémiologie et Santé des Populations), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.; Institut Gustave Roussy, Villejuif, France. (författare)
Severi, GianlucaCESP (Centre de Recherche en Epidémiologie et Santé des Populations), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.; Institut Gustave Roussy, Villejuif, France. (författare)
Carbonnel, FranckCESP (Centre de Recherche en Epidémiologie et Santé des Populations), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.; Institut Gustave Roussy, Villejuif, France.; Department of Gastroenterology, Bicêtre University Hospital, Public Assistance Hospitals of Paris, Le Kremlin Bicêtre, France. (författare)
Katzke, VerenaDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. (författare)
Boeing, HeinerDepartment of Epidemiology, German Institute of Human Nutrition Postdam-Rehbrücke, Nuthetal, Germany. (författare)
Bergmann, Manuela M.Department of Epidemiology, German Institute of Human Nutrition Postdam-Rehbrücke, Nuthetal, Germany. (författare)
Trichopoulou, AntoniaHellenic Health Foundation, Athens, Greece. (författare)
Karakatsani, AnnaHellenic Health Foundation, Athens, Greece.; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Haidari, Greece. (författare)
Martimianaki, GeorgiaHellenic Health Foundation, Athens, Greece. (författare)
Palli, DomenicoCancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy.,Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. (författare)
Tagliabue, GiovannaLombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. (författare)
Panico, SalvatoreDipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. (författare)
Tumino, RosarioCancer Registry and Histopathology Department, “M.P. Arezzo” Hospital, ASP Ragusa, Ragusa, Italy. (författare)
Sacerdote, CarlottaKarolinska Institutet (författare)
Skeie, GuriDepartment of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.; Nutritional Epidemiology Group, School of Food and Nutrition, University of Leeds, Leeds, UK. (författare)
Merino, SusanaPublic Health Directorate, Asturias, Spain. (författare)
Bonet, CatalinaCancer Epidemiology Research Program, Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. (författare)
Rodríguez-Barranco, MiguelEscuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, ibs. GRANADA, Universidad de Granada, Granada, Spain.; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. (författare)
Gil, LeirePublic Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, San Sebastian, Spain. (författare)
Chirlaque, Maria-DoloresDepartment of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. (författare)
Ardanaz, EvaNavarra Public Health Institute, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. (författare)
Myte, RobinUmeå universitet,Onkologi,Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.(Swepub:umu)romy0001 (författare)
Hultdin, JohanUmeå universitet,Klinisk kemi,Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.(Swepub:umu)johu0007 (författare)
Perez-Cornago, AuroraCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. (författare)
Aune, DagfinnDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; Department of Nutrition, Bjørknes University College, Oslo, Norway.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. (författare)
Tsilidis, Konstantinos K.Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. (författare)
Albanes, DemetriusDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (författare)
Baron, John A.Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. (författare)
Berndt, Sonja I.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (författare)
Bézieau, StéphaneService de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.,Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. (författare)
Brenner, HermannDivision 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. (författare)
Campbell, Peter T.Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. (författare)
Casey, GrahamCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA. (författare)
Chan, Andrew T.Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.;Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. (författare)
Chang-Claude, JennyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. (författare)
Chanock, Stephen J.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (författare)
Cotterchio, MichellePrevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada.; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. (författare)
Gallinger, StevenLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. (författare)
Gruber, Stephen B.Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. (författare)
Haile, Robert W.Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. (författare)
Hampe, JochenDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. (författare)
Hoffmeister, MichaelDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. (författare)
Hopper, John L.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. (författare)
Hsu, LiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Biostatistics, University of Washington, Seattle, WA, USA. (författare)
Huyghe, Jeroen R.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (författare)
Jenkins, Mark A.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. (författare)
Joshi, Amit D.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (författare)
Kampman, EllenDivision of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands. (författare)
Larsson, Susanna C.Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.(Swepub:uu)susla720 (författare)
Le Marchand, LoicUniversity of Hawaii Cancer Center, Honolulu, HI, USA. (författare)
Li, Christopher I.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (författare)
Li, LiDepartment of Family Medicine, University of Virginia, Charlottesville, VA, USA.,Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.,Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. (författare)
Lindblom, AnnikaKarolinska Institutet (författare)
Lindor, Noralane M.Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. (författare)
Martín, VicenteCIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Biomedicine Institute (IBIOMED), University of León, León, Spain. (författare)
Moreno, VictorColorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat, Barcelona, Spain.; Cancer Epidemiology Research Program, Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. (författare)
Newcomb, Polly A.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA. (författare)
Offit, KennethClinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.; Department of Medicine, Weill Cornell Medical College, New York, USA. (författare)
Ogino, ShujiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. (författare)
Parfrey, Patrick S.The Clinical Epidemiology Unit, Memorial University Medical School, Newfoundland, Canada. (författare)
Pharoah, Paul D. P.Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. (författare)
Rennert, GadDepartment of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Clalit National Cancer Control Center, Haifa, Israel. (författare)
Sakoda, Lori C.Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (författare)
Schafmayer, ClemensDepartment of General, Visceral, Vascular, and Transplantation Surgery, University Hospital Rostock, Rostock, Germany. (författare)
Schmit, Stephanie L.Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. (författare)
Schoen, Robert E.Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. (författare)
Slattery, Martha L.Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. (författare)
Thibodeau, Stephen N.Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. (författare)
Ulrich, Cornelia M.Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. (författare)
van Duijnhoven, Franzel J. B.Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands. (författare)
Weigl, KorbinianDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Medical Faculty, University of Heidelberg, Heidelberg, Germany. (författare)
Weinstein, Stephanie J.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (författare)
White, EmilyPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA. (författare)
Wolk, AlicjaKarolinska Institutet (författare)
Woods, Michael O.Discipline of Genetics, Memorial University of Newfoundland, St. John’s, Canada. (författare)
Wu, Anna H.University of Southern California, Preventative Medicine, Los Angeles, CA, USA. (författare)
Zhang, XuehongChanning Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. (författare)
Ferrari, PietroNutritional Methodology and Biostatistics Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69372, Lyon CEDEX 08, France. (författare)
Anton, GabrieleInstitute of Epidemiology, Helmholtz Zentrum Munich, Neuherberg, Germany. (författare)
Peters, AnnetteInstitute of Epidemiology, Helmholtz Zentrum Munich, Neuherberg, Germany. (författare)
Peters, UlrikePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA. (författare)
Gunter, Marc J.Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. (författare)
Wagner, Karl-HeinzDepartment of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria. (författare)
Freisling, HeinzNutritional Methodology and Biostatistics Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69372, Lyon CEDEX 08, France. (författare)
Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria.Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. (creator_code:org_t)

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