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.T. 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

doi:10.1016/j.xhgg.2020.100010

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 HardikarChristopher 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.T. 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

^*Corresponding author for this work

Nutrition and Disease

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

3 Citations (Scopus)

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
Article number	100010
Journal	Human Genetics and Genomics Advances
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.xhgg.2020.100010
Publication status	Published - 22 Oct 2020

Keywords

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

UN SDGs

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

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Jarvik, G. P., Wang, X., Fontanillas, P., Kim, E., Chanprasert, S., Gordon, A. S., Bastarache, L., Kowdley, K. V., Harrison, T., Rosenthal, E. A., Stanaway, I. B., Bézieau, S., Weinstein, S. J., Newcomb, P. A., Casey, G., Platz, E. A., Visvanathan, K., Le Marchand, L., Ulrich, C. M., ... Tangen, C. M. (2020). Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis. Human Genetics and Genomics Advances, 1(1), Article 100010. https://doi.org/10.1016/j.xhgg.2020.100010

@article{b79ee69df3c44db4ace7800d2bbb014a,

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

author = "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 D.T. Bishop 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.}",

year = "2020",

month = oct,

day = "22",

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

language = "English",

volume = "1",

journal = "Human Genetics and Genomics Advances",

issn = "2666-2477",

publisher = "Cell Press",

number = "1",

}

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, 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 2020, 'Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis', Human Genetics and Genomics Advances, vol. 1, no. 1, 100010. https://doi.org/10.1016/j.xhgg.2020.100010

TY - JOUR

T1 - Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis

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.T.

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 - age of onset

KW - colon cancer

KW - ferritin

KW - genetic

KW - HFE gene

KW - iron

KW - population screening

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 -

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

Abstract

Keywords

UN SDGs

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