TY - JOUR
T1 - Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis
AU - 23andMe Research Team
AU - Jarvik, Gail P.
AU - Wang, Xiaoliang
AU - Fontanillas, Pierre
AU - Kim, Esther
AU - Chanprasert, Sirisak
AU - Gordon, Adam S.
AU - Bastarache, Lisa
AU - Kowdley, Kris V.
AU - Harrison, Tabitha
AU - Rosenthal, Elisabeth A.
AU - Stanaway, Ian B.
AU - Bézieau, Stéphane
AU - Weinstein, Stephanie J.
AU - Newcomb, Polly A.
AU - Casey, Graham
AU - Platz, Elizabeth A.
AU - Visvanathan, Kala
AU - Le Marchand, Loic
AU - Ulrich, Cornelia M.
AU - Hardikar, Sheetal
AU - Li, Christopher I.
AU - van Duijnhoven, Franzel J.B.
AU - Gsur, Andrea
AU - Campbell, Peter T.
AU - Moreno, Victor
AU - Vodička, Pavel
AU - Brenner, Hermann
AU - Chang-Claude, Jenny
AU - Hoffmeister, Michael
AU - Slattery, Martha L.
AU - Gunter, Marc J.
AU - Aglago, Elom K.
AU - Castellví-Bel, Sergi
AU - Kweon, Sun Seog
AU - Chan, Andrew T.
AU - Li, Li
AU - Zheng, Wei
AU - Bishop, D. Timothy
AU - Giles, Graham G.
AU - Rennert, Gad
AU - Offit, Kenneth
AU - Keku, Temitope O.
AU - Woods, Michael O.
AU - Hampe, Jochen
AU - Van Guelpen, Bethan
AU - Gallinger, Steven J.
AU - de la Chapelle, Albert
AU - Hampel, Heather
AU - Berndt, Sonja I.
AU - Tangen, Catherine M.
N1 - Funding Information:
This work was supported by National Human Genome Research Institute (NHGRI; U01HG008657 ). Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) funding includes that from the National Cancer Institute (NCI) U01 CA137088 , R01 CA059045 , R01201407 , and P30 CA015704 . GECCO genotyping services were provided by the Center for Inherited Disease Research (CIDR; X01-HG008596 and X-01-HG007585 ). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract HHSN268201200008I . We would like to thank all CRC studies’ and 23andMe research participants and employees for making this work possible. Additional colon cancer consortia acknowledgments are in supplemental acknowledgments .
Funding Information:
This work was supported by National Human Genome Research Institute (NHGRI; U01HG008657). Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) funding includes that from the National Cancer Institute (NCI) U01 CA137088, R01 CA059045, R01201407, and P30 CA015704. GECCO genotyping services were provided by the Center for Inherited Disease Research (CIDR; X01-HG008596 and X-01-HG007585). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract HHSN268201200008I. We would like to thank all CRC studies’ and 23andMe research participants and employees for making this work possible. Additional colon cancer consortia acknowledgments are in supplemental acknowledgments. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. D.R.C. is a paid consultant for UnitedHealth Group Research and Development. H.H. is on the Scientific Advisory Boards of Invitae Genetics, Genome Medical, and Promega. She is a consultant for 23and Me. She conducts collaborative research with Invitae Genetics, Myriad Genetic Laboratories, and Ambry Genetics. She holds stocks in Genome Medical. J.M. P.F. E.K. and members of the 23andMe Research Team are current or former employees of 23andMe and hold stock or stock options in 23andMe. S.B.G. is a founder of Brogent International with equity.
Publisher Copyright:
© 2020 The Authors
PY - 2020/10/22
Y1 - 2020/10/22
N2 - 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.
AB - 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.
KW - HFE gene
KW - age of onset
KW - colon cancer
KW - ferritin
KW - genetic
KW - iron
KW - population screening
UR - http://www.scopus.com/inward/record.url?scp=85112000683&partnerID=8YFLogxK
U2 - 10.1016/j.xhgg.2020.100010
DO - 10.1016/j.xhgg.2020.100010
M3 - Article
AN - SCOPUS:85112000683
SN - 2666-2477
VL - 1
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
IS - 1
M1 - 100010
ER -