Background: MUTYH associated polyposis (MAP) is a recessive trait characterised by multiple colorectal adenomas and a high risk of colorectal cancer. MUTYH functions in the DNA base excision repair pathway and has a key role in the repair of oxidative DNA damage.
Objectives: To assess the contribution of inherited variants in genes involved in base excision repair and oxidative DNA damage including MUTYH, OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 to the multiple colorectal adenoma phenotype.
Methods: Inherited variants of MUTYH, OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 were sought in 167 unrelated patients with multiple colorectal adenomas whose family histories were consistent with recessive inheritance. We also characterised these variants in ~ 300 population controls.
Results: Thirty three patients (20%) and no controls were MUTYH homozygotes or compound heterozygotes (i.e. carried two mutations) and therefore had MAP. Eight different pathogenic MUTYH mutations were identified of which 4 were novel. MAP cases had significantly more adenomas than non-MAP cases (P=0.0009; Exact test for trends in proportions) and presented earlier (P=0.013; ANOVA). Twenty four protein altering variants were identified upon screening of OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1. However, all combinations of two (or more) variants that were identified at an individual locus in patients were also seen in controls and no variants were significantly over (or under-) represented in cases.
Conclusion: Multiple rare alleles of MUTYH are associated with autosomal recessive MUTYH Associated Polyposis (MAP) whilst OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 do not contribute significantly to autosomal recessive polyposis.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.