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Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH

Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH
Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH
Background & Aims: MUTYH-associated polyposis (MAP) is an autosomal recessive disorder caused by mutations in the MUTYH gene. Patients with MAP are at extremely high risk of colorectal cancer, but the risks of colorectal and other cancers in heterozygous carriers of a single MUTYH mutation are uncertain. We performed a retrospective study of cancer incidence and causes of death among obligate MUTYH heterozygote individuals.
Methods: MAP index cases were identified from polyposis registers in Germany, The Netherlands, and the United Kingdom. Cancer incidence, cancer mortality, and all-cause mortality data were collected from 347 parents of unrelated MAP index cases and the spouses of 3 index cases who were also found to be heterozygous for single MUTYH mutations. These data were compared with appropriate national sex-, age-, and period-specific population data to obtain standardized mortality ratios (SMR) and standardized incidence ratios (SIR).
Results: there was a 2-fold increase in the incidence of colorectal cancer among parents of MAP cases, compared with the general population (SIR, 2.12; 95% confidence interval [CI]: 1.30–3.28). Their colorectal cancer mortality was not increased significantly (SMR, 1.02; 95% CI: 0.41–2.10) nor was overall cancer risk (SIR, 0.92; 95% CI: 0.70–1.18), cancer mortality (SMR, 1.12; 95% CI: 0.83–1.48), or overall mortality (SMR, 0.94; 95% CI: 0.80–1.08).
Conclusions: the risk of colorectal cancer in heterozygous carriers of single MUTYH mutations who are relatives of patients with MAP is comparable with that of first-degree relatives of patients with sporadic colorectal cancer. Screening measures should be based on this modest increase in risk
0016-5085
489-494
Jones, Natalie
bcd9f97a-1348-448b-bfa0-539a2eab59e9
Vogt, Stefanie
0ec69283-3849-42f1-9d6b-23d77103c205
Nielsen, Maartje
9ad206de-97e1-4c37-90eb-d66fe3b602e0
Christian, Daria
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Wark, Petra A.
4a00ff2e-1ee7-4235-9ba8-301ce091958a
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Edwards, Emma
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Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Maher, Eamonn R.
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Vasen, Hans F.
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Hes, Frederik J.
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Aretz, Stefan
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Sampson, Julian R.
3c5832fb-abbb-4781-b931-5b5acd579466
Jones, Natalie
bcd9f97a-1348-448b-bfa0-539a2eab59e9
Vogt, Stefanie
0ec69283-3849-42f1-9d6b-23d77103c205
Nielsen, Maartje
9ad206de-97e1-4c37-90eb-d66fe3b602e0
Christian, Daria
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Wark, Petra A.
4a00ff2e-1ee7-4235-9ba8-301ce091958a
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Edwards, Emma
098e0345-ce64-40b8-9233-b94fb80425ea
Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Maher, Eamonn R.
577b8856-f8a8-49c2-9484-288d9f964aed
Vasen, Hans F.
2edf2c67-6263-4557-87cc-0cc9eede4dfb
Hes, Frederik J.
46f24ec7-9fbd-4a38-a1d3-ffb0473d4e0c
Aretz, Stefan
d3d576f6-87ac-43e7-a5c2-9e9e0cbef38b
Sampson, Julian R.
3c5832fb-abbb-4781-b931-5b5acd579466

Jones, Natalie, Vogt, Stefanie, Nielsen, Maartje, Christian, Daria, Wark, Petra A., Eccles, Diana, Edwards, Emma, Evans, D. Gareth, Maher, Eamonn R., Vasen, Hans F., Hes, Frederik J., Aretz, Stefan and Sampson, Julian R. (2002) Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. Gastroenterology, 137 (2), 489-494. (doi:10.1053/j.gastro.2009.04.047).

Record type: Article

Abstract

Background & Aims: MUTYH-associated polyposis (MAP) is an autosomal recessive disorder caused by mutations in the MUTYH gene. Patients with MAP are at extremely high risk of colorectal cancer, but the risks of colorectal and other cancers in heterozygous carriers of a single MUTYH mutation are uncertain. We performed a retrospective study of cancer incidence and causes of death among obligate MUTYH heterozygote individuals.
Methods: MAP index cases were identified from polyposis registers in Germany, The Netherlands, and the United Kingdom. Cancer incidence, cancer mortality, and all-cause mortality data were collected from 347 parents of unrelated MAP index cases and the spouses of 3 index cases who were also found to be heterozygous for single MUTYH mutations. These data were compared with appropriate national sex-, age-, and period-specific population data to obtain standardized mortality ratios (SMR) and standardized incidence ratios (SIR).
Results: there was a 2-fold increase in the incidence of colorectal cancer among parents of MAP cases, compared with the general population (SIR, 2.12; 95% confidence interval [CI]: 1.30–3.28). Their colorectal cancer mortality was not increased significantly (SMR, 1.02; 95% CI: 0.41–2.10) nor was overall cancer risk (SIR, 0.92; 95% CI: 0.70–1.18), cancer mortality (SMR, 1.12; 95% CI: 0.83–1.48), or overall mortality (SMR, 0.94; 95% CI: 0.80–1.08).
Conclusions: the risk of colorectal cancer in heterozygous carriers of single MUTYH mutations who are relatives of patients with MAP is comparable with that of first-degree relatives of patients with sporadic colorectal cancer. Screening measures should be based on this modest increase in risk

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Published date: August 2002

Identifiers

Local EPrints ID: 69921
URI: http://eprints.soton.ac.uk/id/eprint/69921
ISSN: 0016-5085
PURE UUID: 563b1d18-fb3d-44b7-b3e4-0d78b890cad1

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Date deposited: 10 Dec 2009
Last modified: 19 Jul 2019 23:46

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Contributors

Author: Natalie Jones
Author: Stefanie Vogt
Author: Maartje Nielsen
Author: Daria Christian
Author: Petra A. Wark
Author: Diana Eccles
Author: Emma Edwards
Author: D. Gareth Evans
Author: Eamonn R. Maher
Author: Hans F. Vasen
Author: Frederik J. Hes
Author: Stefan Aretz
Author: Julian R. Sampson

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