Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3

摘要: Background: MUTYH-associated polyposis (MAP) is a recessive trait characterised by multiple colorectal adenomas and high risk of cancer. MUTYH functions in the DNA base excision repair pathway has key role oxidative damage. Objectives: To assess contribution inherited variants genes involved damage including MUTYH, OGG1, NEIL1, NEIL2, NEIL3, NUDT1 NTH1 to adenoma phenotype. Methods: Inherited were sought 167 unrelated patients with whose family histories consistent inheritance. These also ∼300 population controls. Results: Thirty-three (20%) no controls homozygotes or compound heterozygotes (ie, carried two mutations) therefore had MAP. Eight different pathogenic mutations identified, which four novel. MAP cases significantly more than non-MAP (p = 0.0009; exact test for trends proportions) presented earlier (p = 0.013; analysis variance). Twenty-four protein-altering identified upon screening NTH1. However, all combinations (or more) that at an individual locus seen controls, over-represented under-represented) cases. Conclusion: Multiple rare alleles are associated autosomal MAP, while do not contribute polyposis.