Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer.
Sci Rep
; 5: 14060, 2015 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-26358404
ABSTRACT
Bloom syndrome is an autosomal recessive disorder characterized by chromosomal instability and increased cancer risk, caused by biallelic mutations in the RECQL-helicase gene BLM. Previous studies have led to conflicting conclusions as to whether carriers of heterozygous BLM mutations have an increased risk to develop colorectal cancer (CRC). We recently identified two carriers of a pathogenic BLM mutation in a cohort of 55 early-onset CRC patients (≤45 years of age), suggesting an overrepresentation compared to the normal population. Here, we performed targeted sequencing using molecular inversion probes to screen an additional cohort of 185 CRC patients (≤50 years of age) and 532 population-matched controls for deleterious BLM mutations. In total, we identified three additional CRC patients (1.6%) and one control individual (0.2%) that carried a known pathogenic BLM mutation, suggesting that these mutations are enriched in early-onset CRC patients (P = 0.05516). A comparison with local and publically available databases from individuals without suspicion for hereditary cancer confirmed this enrichment (P = 0.003534). Analysis of family members of the five BLM mutation carriers with CRC suggests an incomplete penetrance for CRC development. Therefore, these data indicate that carriers of deleterious BLM mutations are at increased risk to develop CRC, albeit with a moderate-to-low penetrance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Mutação em Linhagem Germinativa
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RecQ Helicases
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Risk_factors_studies
/
Screening_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Holanda
País de publicação:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM