Monoallelic NTHL1 Loss-of-Function Variants and Risk of Polyposis and Colorectal Cancer.

The endonuclease III-like protein 1, encoded by NTHL1, is a bifunctional glycosylase involved in base-excision repair (BER) that recognizes and removes oxidized pyrimidines.1 Similar to biallelic loss-of-function (LoF) variants in MUTYH,2 biallelic LoF variants in NTHL1 predispose to colorectal polyps and colorectal cancer (CRC).3 Recently, a multitumor phenotype was observed in individuals diagnosed with NTHL1 deficiency.4 Carriers of monoallelic pathogenic variants in MUTYH have an increased, albeit small, risk of CRC.