A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.
Br J Cancer
; 103(12): 1875-84, 2010 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-21063410
ABSTRACT
BACKGROUND:
defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants and investigate age and sex influence on risk.METHODS:
MUTYH genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested a crude model; adjusted for age and sex; adjusted for age, sex and study.RESULTS:
all three models produced very similar results. MUTYH bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI) 6.95-115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI 1.00-1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI 5.02-23.2; OR=6.47, 95% CI 2.33-18.0; OR=3.35, 95% CI 1.14-9.89) and marginal mono-allelic effect for variants MUTYH (OR=1.16, 95% CI 1.00-1.34) and Y179C alone (OR=1.34, 95% CI 1.01-1.77).CONCLUSIONS:
overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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DNA Glicosilases
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article