Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis.
J Med Genet
; 51(1): 55-60, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24253443
ABSTRACT
BACKGROUND:
Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas.METHODS:
We analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs).RESULTS:
We found a statistically significant association with two of the variants tested rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC.CONCLUSIONS:
These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 11
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Cromossomos Humanos Par 15
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Neoplasias Colorretais
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Aberrações Cromossômicas
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Polipose Adenomatosa do Colo
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article