Association between monoallelic MUTYH mutation and colorectal cancer risk: a meta-regression analysis

Fam Cancer. 2011 Mar;10(1):1-9. doi: 10.1007/s10689-010-9399-5.


Whether people who inherit a mutation in MUTYH from only one parent (monoallelic mutation) are at increased risk of colorectal cancer (CRC) remains controversial. Most previous studies and meta-analyses have not found statistically significant associations but, given carriers are relatively rare, may be underpowered to detect small increased risks. We have conducted a systematic review and meta-regression analysis of previously published case-control studies to estimate the strength of association for monoallelic MUTYH mutation and CRC risk. Potential sources of heterogeneity were evaluated. We have compared the carrier frequency in cases with a family history of CRC to that of controls, as a novel and powerful design, to measure statistical evidence of an association but not the strength of association. The magnitude of the genotype-disease association, estimated from a pooled odds ratio comparing cases unselected for family history with controls, was 1.15 (95% CI = 0.98-1.36) and not substantially altered by adjustment for potential sources of heterogeneity. Monoallelic mutation carrier frequency was greater for cases ascertained due to a family history (3.3%; SE 0.9%) than for controls (1.4%; SE 0.3%) (P = 0.02). Monoallelic MUTYH mutation carriers are at increased risk of CRC but the average increase is small.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Alleles
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / genetics*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Mutation / genetics*


  • DNA Glycosylases
  • mutY adenine glycosylase