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

23andMe Research Team

doi:10.1016/j.xhgg.2020.100010

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

23andMe Research Team

Pharmacology

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Article number	100010
Journal	Human Genetics and Genomics Advances
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.xhgg.2020.100010
State	Published - Oct 22 2020

Funding

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 . 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.

Keywords

HFE gene
age of onset
colon cancer
ferritin
genetic
iron
population screening

ASJC Scopus subject areas

Molecular Medicine
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xhgg.2020.100010

Cite this

@article{eac4585529714420aaf80b9aaa334af0,

title = "Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis",

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.",

keywords = "HFE gene, age of onset, colon cancer, ferritin, genetic, iron, population screening",

author = "{23andMe Research Team} and Jarvik, {Gail P.} and Xiaoliang Wang and Pierre Fontanillas and Esther Kim and Sirisak Chanprasert and Gordon, {Adam S.} and Lisa Bastarache and Kowdley, {Kris V.} and Tabitha Harrison and Rosenthal, {Elisabeth A.} and Stanaway, {Ian B.} and St{\'e}phane B{\'e}zieau and Weinstein, {Stephanie J.} and Newcomb, {Polly A.} and Graham Casey and Platz, {Elizabeth A.} and Kala Visvanathan and {Le Marchand}, Loic and Ulrich, {Cornelia M.} and Sheetal Hardikar and Li, {Christopher I.} and {van Duijnhoven}, {Franzel J.B.} and Andrea Gsur and Campbell, {Peter T.} and Victor Moreno and Pavel Vodi{\v c}ka and Hermann Brenner and Jenny Chang-Claude and Michael Hoffmeister and Slattery, {Martha L.} and Gunter, {Marc J.} and Aglago, {Elom K.} and Sergi Castellv{\'i}-Bel and Kweon, {Sun Seog} and Chan, {Andrew T.} and Li Li and Wei Zheng and Bishop, {D. Timothy} and Giles, {Graham G.} and Gad Rennert and Kenneth Offit and Keku, {Temitope O.} and Woods, {Michael O.} and Jochen Hampe and {Van Guelpen}, Bethan and Gallinger, {Steven J.} and {de la Chapelle}, Albert and Heather Hampel and Berndt, {Sonja I.} and Tangen, {Catherine M.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = oct,

day = "22",

doi = "10.1016/j.xhgg.2020.100010",

language = "English (US)",

volume = "1",

journal = "Human Genetics and Genomics Advances",

issn = "2666-2477",

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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.

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

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UR - http://www.scopus.com/inward/citedby.url?scp=85112000683&partnerID=8YFLogxK

U2 - 10.1016/j.xhgg.2020.100010

DO - 10.1016/j.xhgg.2020.100010

M3 - Article

C2 - 35047832

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 -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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