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

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.