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Title: A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants
Author: Theodoratou, Evropi
Campbell, Harry
Tenesa, Albert
Houlston, Richard S.
Webb Youdale, Susan
Lubbe, Steven
Broderick, Peter
Gallinger, Steven
Croitoru, Marina E.
Jenkins, Mark A.
Win, Aung K.
Cleary, Sean
Koessler, Thibaud
Pharoah, Paul D. P.
Küry, Sébastien
Bézieau, Stéphane
Buecher, Bruno
Ellis, Nathan A.
Peterlongo, Paolo
Offit, Kenneth
Aaltonen, Lauri A.
Enholm, Susa
Lindblom, Annika
Zhou, X.L.
Tomlinson, Ian P.
Moreno Aguado, Víctor
Blanco Guillermo, Ignacio
Capellá, G. (Gabriel)
Barnetson, Rebecca
Porteous, Mary E.
Dunlop, Malcolm
Farrington, Susan M.
Keywords: Càncer colorectal
Colorectal cancer
Issue Date: 7-Dec-2010
Publisher: Cancer Research UK
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 A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89)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.
Note: Versió postprint del document publicat a:
It is part of: British Journal of Cancer, 2010, vol. 103, num. 12, p. 1875-1884
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ISSN: 0007-0920
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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