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

Theodoratou E, Campbell H, Tenesa A, Houlston R, Webb E, Lubbe S, Broderick P, Gallinger S, Croitoru EM, Jenkins MA, Win AK, Cleary SP, Koessler T, Pharoah PD, Küry S, Bézieau S, Buecher B, Ellis NA, Peterlongo P, Offit K, Aaltonen LA, Enholm S, Lindblom A, Zhou XL, Tomlinson IP, Moreno V, Blanco I, Capellà G, Barnetson R, Porteous ME, Dunlop MG, Farrington SM - Br. J. Cancer (2010)

Bottom Line: Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. all three models produced very similar results.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effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00-1.80).A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89)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). overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers.

View Article: PubMed Central - PubMed

Affiliation: Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

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Meta-analysis of studies comparing MUTYH WM vs WW. SOCCS data include Farrington et al (2005), Tenesa et al (2006) and unpublished data from the SOCCS study obtained in 2008; Cleary data include Croitoru et al (2004); Lubbe data include Webb et al (2006) and Fleischmann et al (2004). Unpublished studies included are Tomilson I (2006) and Koessler T (2007).
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fig2: Meta-analysis of studies comparing MUTYH WM vs WW. SOCCS data include Farrington et al (2005), Tenesa et al (2006) and unpublished data from the SOCCS study obtained in 2008; Cleary data include Croitoru et al (2004); Lubbe data include Webb et al (2006) and Fleischmann et al (2004). Unpublished studies included are Tomilson I (2006) and Koessler T (2007).

Mentions: The results of a meta-analysis of published and unpublished datasets submitted to us, estimating the effect of the MUTYH whole gene defects demonstrated a pooled fixed bi-allelic effect of 10.8 (95% CI: 5.02–23.2) for the MM and a pooled fixed mono-allelic effect of 1.16 (95% CI: 1.00–1.34) for WM genotype (Table 3; Figures 1 and 2). Analysis of the specific variants by pooled meta-analysis demonstrated bi-allelic effects for both G396D and Y179C (OR=6.47 (95% CI: 2.33–18.0) and OR=3.35 (95% CI: 1.14–9.89), respectively) and in agreement with the logistic regression analysis results, Y179C variant also demonstrated a very similar pooled fixed mono-allelic effect of 1.34 (95% CI: 1.01–1.77; Tables 4 and 5; Supplementary Figures 1–4).


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

Theodoratou E, Campbell H, Tenesa A, Houlston R, Webb E, Lubbe S, Broderick P, Gallinger S, Croitoru EM, Jenkins MA, Win AK, Cleary SP, Koessler T, Pharoah PD, Küry S, Bézieau S, Buecher B, Ellis NA, Peterlongo P, Offit K, Aaltonen LA, Enholm S, Lindblom A, Zhou XL, Tomlinson IP, Moreno V, Blanco I, Capellà G, Barnetson R, Porteous ME, Dunlop MG, Farrington SM - Br. J. Cancer (2010)

Meta-analysis of studies comparing MUTYH WM vs WW. SOCCS data include Farrington et al (2005), Tenesa et al (2006) and unpublished data from the SOCCS study obtained in 2008; Cleary data include Croitoru et al (2004); Lubbe data include Webb et al (2006) and Fleischmann et al (2004). Unpublished studies included are Tomilson I (2006) and Koessler T (2007).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008602&req=5

fig2: Meta-analysis of studies comparing MUTYH WM vs WW. SOCCS data include Farrington et al (2005), Tenesa et al (2006) and unpublished data from the SOCCS study obtained in 2008; Cleary data include Croitoru et al (2004); Lubbe data include Webb et al (2006) and Fleischmann et al (2004). Unpublished studies included are Tomilson I (2006) and Koessler T (2007).
Mentions: The results of a meta-analysis of published and unpublished datasets submitted to us, estimating the effect of the MUTYH whole gene defects demonstrated a pooled fixed bi-allelic effect of 10.8 (95% CI: 5.02–23.2) for the MM and a pooled fixed mono-allelic effect of 1.16 (95% CI: 1.00–1.34) for WM genotype (Table 3; Figures 1 and 2). Analysis of the specific variants by pooled meta-analysis demonstrated bi-allelic effects for both G396D and Y179C (OR=6.47 (95% CI: 2.33–18.0) and OR=3.35 (95% CI: 1.14–9.89), respectively) and in agreement with the logistic regression analysis results, Y179C variant also demonstrated a very similar pooled fixed mono-allelic effect of 1.34 (95% CI: 1.01–1.77; Tables 4 and 5; Supplementary Figures 1–4).

Bottom Line: Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. all three models produced very similar results.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). overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers.

View Article: PubMed Central - PubMed

Affiliation: Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Show MeSH
Related in: MedlinePlus