A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.
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effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00-1.80).A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89)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.
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
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Mentions: The results of a meta-analysis of published and unpublished datasets submitted to us, estimating the effect of the MUTYH whole gene defects demonstrated a pooled fixed bi-allelic effect of 10.8 (95% CI: 5.02–23.2) for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).
Affiliation: Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.