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Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis.

About this Publication
Title
Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis.
Pubmed ID
35047832 (View this publication on the PubMed website)
Digital Object Identifier
Publication
HGG Adv. 2020 Oct 22; Volume 1 (Issue 1): Pages 100010
Authors
Jarvik GP, Wang X, Fontanillas P, Kim E, Chanprasert S, Gordon AS, Bastarache L, Kowdley KV, Harrison T, Rosenthal EA, Stanaway IB, Bézieau S, Weinstein SJ, Newcomb PA, Casey G, Platz EA, Visvanathan K, Le Marchand L, Ulrich CM, Hardikar S, ...show more Li CI, van Duijnhoven FJB, Gsur A, Campbell PT, Moreno V, Vodička P, Brenner H, Chang-Claude J, Hoffmeister M, Slattery ML, Gunter MJ, Aglago EK, Castellví-Bel S, Kweon SS, Chan AT, Li L, Zheng W, Bishop DT, Giles GG, Rennert G, Offit K, Keku TO, Woods MO, Hampe J, Van Guelpen B, Gallinger SJ, de la Chapelle A, Hampel H, Berndt SI, Tangen CM, Lindblom A, Wolk A, Burnett-Hartman A, Wu AH, White E, 23andMe Research Team, Gruber SB, Jenkins MA, Mountain J, Peters U, Crosslin DR
Affiliations
  • University of Washington Medical Center, Seattle, WA, USA.
  • Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • 23andMe, Sunnyvale, CA, USA.
  • Northwestern University, Evanston, IL, USA.
  • Vanderbilt Medical Center, Atlanta, GA, USA.
  • Liver Institute Northwest, Seattle, WA, USA.
  • Centre Hospitalier Universitaire (CHU) Nantes, France.
  • National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • University of Virginia, Charlottesville, VA, USA.
  • Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
...show more
  • University of Hawaii Cancer Center, Honolulu, HI, USA.
  • University of Utah, Salt Lake City, UT, USA.
  • Division of Human Nutrition and Health, Wageningen University and Research Wageningen, the Netherlands.
  • Medical University Vienna, Vienna, Austria.
  • American Cancer Society, Atlanta, GA, USA.
  • 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.
  • Institute of Experimental Medicine, Czech Academy of Sciences, Biomedical Center, Medical Faculty Pilsen and 1st Medical Faculty, Charles University, Prague, Czech Republic.
  • German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
  • 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.
  • Chonnam National University Medical School, Gwangju, Korea.
  • Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • University of Leeds, Leeds, UK.
  • Cancer Council Victoria, Melbourne, VIC, Australia.
  • Lady Davis Carmel Medical Center, Haifa, Israel.
  • Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • University of North Carolina, Chapel Hill, NC, USA.
  • Memorial University of Newfoundland, St. John's, NL, Canada.
  • Technische Universität Dresden (TU Dresden), Dresden, Germany.
  • Department of Radiation Sciences, Oncology, Umeå University and Wallenberg Centre for Molecular Medicine, Umeå University, Sweden.
  • University of Toronto, Toronto, ON, Canada.
  • The Ohio State University, Columbus, OH, USA.
  • Karolinska University Hospital, Stockholm, Sweden.
  • Karolinska Institutet, Stockholm, Sweden.
  • Kaiser Permanente Colorado, Denver, CO, USA.
  • University of Southern California, Los Angeles, CA, USA.
  • City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, VIC, Australia.
Abstract

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.

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