HGG Advances (Oct 2020)
Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis
- Gail P. Jarvik,
- Xiaoliang Wang,
- Pierre Fontanillas,
- Esther Kim,
- Sirisak Chanprasert,
- Adam S. Gordon,
- Lisa Bastarache,
- Kris V. Kowdley,
- Tabitha Harrison,
- Elisabeth A. Rosenthal,
- Ian B. Stanaway,
- Stéphane Bézieau,
- Stephanie J. Weinstein,
- Polly A. Newcomb,
- Graham Casey,
- Elizabeth A. Platz,
- Kala Visvanathan,
- Loic Le Marchand,
- Cornelia M. Ulrich,
- Sheetal Hardikar,
- Christopher I. Li,
- Franzel J.B. van Duijnhoven,
- Andrea Gsur,
- Peter T. Campbell,
- Victor Moreno,
- Pavel Vodička,
- Hermann Brenner,
- Jenny Chang-Claude,
- Michael Hoffmeister,
- Martha L. Slattery,
- Marc J. Gunter,
- Elom K. Aglago,
- Sergi Castellví-Bel,
- Sun-Seog Kweon,
- Andrew T. Chan,
- Li Li,
- Wei Zheng,
- D. Timothy Bishop,
- Graham G. Giles,
- Gad Rennert,
- Kenneth Offit,
- Temitope O. Keku,
- Michael O. Woods,
- Jochen Hampe,
- Bethan Van Guelpen,
- Steven J. Gallinger,
- Albert de la Chapelle,
- Heather Hampel,
- Sonja I. Berndt,
- Catherine M. Tangen,
- Annika Lindblom,
- Alicja Wolk,
- Andrea Burnett-Hartman,
- Anna H. Wu,
- Emily White,
- Stephen B. Gruber,
- Mark A. Jenkins,
- Joanna Mountain,
- Ulrike Peters,
- David R. Crosslin
Affiliations
- Gail P. Jarvik
- University of Washington Medical Center, Seattle, WA, USA; Corresponding author
- Xiaoliang Wang
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Pierre Fontanillas
- 23andMe, Sunnyvale, CA, USA
- Esther Kim
- 23andMe, Sunnyvale, CA, USA
- Sirisak Chanprasert
- University of Washington Medical Center, Seattle, WA, USA
- Adam S. Gordon
- Northwestern University, Evanston, IL, USA
- Lisa Bastarache
- Vanderbilt Medical Center, Atlanta, GA, USA
- Kris V. Kowdley
- Liver Institute Northwest, Seattle, WA, USA
- Tabitha Harrison
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Elisabeth A. Rosenthal
- University of Washington Medical Center, Seattle, WA, USA
- Ian B. Stanaway
- University of Washington Medical Center, Seattle, WA, USA
- Stéphane Bézieau
- Centre Hospitalier Universitaire (CHU) Nantes, France
- Stephanie J. Weinstein
- National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Polly A. Newcomb
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA; School of Public Health, University of Washington, Seattle, WA
- Graham Casey
- University of Virginia, Charlottesville, VA, USA
- Elizabeth A. Platz
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Kala Visvanathan
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Loic Le Marchand
- University of Hawaii Cancer Center, Honolulu, HI, USA
- Cornelia M. Ulrich
- University of Utah, Salt Lake City, UT, USA
- Sheetal Hardikar
- University of Utah, Salt Lake City, UT, USA
- Christopher I. Li
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Franzel J.B. van Duijnhoven
- Division of Human Nutrition and Health, Wageningen University and Research Wageningen, the Netherlands
- Andrea Gsur
- Medical University Vienna, Vienna, Austria
- Peter T. Campbell
- American Cancer Society, Atlanta, GA, USA
- Victor Moreno
- Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), L’Hospitalet, 08908, Barcelona, Spain
- Pavel Vodička
- Institute of Experimental Medicine, Czech Academy of Sciences, Biomedical Center, Medical Faculty Pilsen and 1st Medical Faculty, Charles University, Prague, Czech Republic
- Hermann Brenner
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Jenny Chang-Claude
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Michael Hoffmeister
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Martha L. Slattery
- University of Utah, Salt Lake City, UT, USA
- Marc J. Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Elom K. Aglago
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Sergi Castellví-Bel
- Gastroenterology Department, 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
- Sun-Seog Kweon
- Chonnam National University Medical School, Gwangju, Korea
- Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Li Li
- University of Virginia, Charlottesville, VA, USA
- Wei Zheng
- Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- D. Timothy Bishop
- University of Leeds, Leeds, UK
- Graham G. Giles
- Cancer Council Victoria, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia; Monash University, Melbourne, VIC, Australia
- Gad Rennert
- Lady Davis Carmel Medical Center, Haifa, Israel
- Kenneth Offit
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Temitope O. Keku
- University of North Carolina, Chapel Hill, NC, USA
- Michael O. Woods
- Memorial University of Newfoundland, St. John’s, NL, Canada
- Jochen Hampe
- Technische Universität Dresden (TU Dresden), Dresden, Germany
- Bethan Van Guelpen
- Department of Radiation Sciences, Oncology, Umeå University and Wallenberg Centre for Molecular Medicine, Umeå University, Sweden
- Steven J. Gallinger
- University of Toronto, Toronto, ON, Canada
- Albert de la Chapelle
- The Ohio State University, Columbus, OH, USA
- Heather Hampel
- The Ohio State University, Columbus, OH, USA
- Sonja I. Berndt
- National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Catherine M. Tangen
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Annika Lindblom
- Karolinska University Hospital, Stockholm, Sweden
- Alicja Wolk
- Karolinska Institutet, Stockholm, Sweden; Uppsala University, Uppsala, Sweden
- Andrea Burnett-Hartman
- Kaiser Permanente Colorado, Denver, CO, USA
- Anna H. Wu
- University of Southern California, Los Angeles, CA, USA
- Emily White
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Stephen B. Gruber
- City of Hope Comprehensive Cancer Center, Duarte, CA, USA
- Mark A. Jenkins
- Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, VIC, Australia
- Joanna Mountain
- 23andMe, Sunnyvale, CA, USA
- Ulrike Peters
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, University of Washington School of Medicine, Seattle, WA, USA
- David R. Crosslin
- University of Washington Medical Center, Seattle, WA, USA
- Journal volume & issue
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Vol. 1,
no. 1
p. 100010
Abstract
Summary: Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91–1.29; p = 0.4) and 1.01 (95% CI, 0.78–1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.
