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A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants

Research output: Contribution to journalArticle

  • R. Houlston
  • E. Webb
  • S. Lubbe
  • P. Broderick
  • S. Gallinger
  • E. M. Croitoru
  • M. A. Jenkins
  • A. K. Win
  • S. P. Cleary
  • T. Koessler
  • P. D. Pharoah
  • S. Kuery
  • S. Bezieau
  • B. Buecher
  • N. A. Ellis
  • P. Peterlongo
  • K. Offit
  • L. A. Aaltonen
  • S. Enholm
  • A. Lindblom
  • V. Moreno
  • I. Blanco
  • G. Capella
  • M. E. Porteous

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Original languageEnglish
Pages (from-to)1875-1884
Number of pages10
JournalBritish Journal of Cancer
Issue number12
Publication statusPublished - 7 Dec 2010


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 A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR = 10.8, 95% CI: 5.02-23.2; OR = 6.47, 95% CI: 2.33-18.0; OR = 3.35, 95% CI: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. British Journal of Cancer (2010) 103, 1875-1884. doi:10.1038/sj.bjc.6605966 www.bjcancer.com Published online 9 November 2010 (C) 2010 Cancer Research UK

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