In a study of 51 individuals with multiple colon polyps drawn from 48 families, genetic testing through whole-exome sequencing identified 7 individuals (from 3 unrelated families) to have a mutation in both copies of their NTHL1 gene, and pedigree structure was consistent with autosomal recessive inheritance.1 All these individuals had colorectal cancer and a large number of adenomas (ranging from 8-50), and none of the 8 cancers or adenomas tested showed microsatellite instability. There were also individuals who developed endometrial and duodenal cancer. A subsequent study of over 2400 families confirmed the association between this gene and colorectal cancer risk.2
1Weren RD, et al. Nat Genet. 2015 Jun. PMID: 25938944.
2Broderick P, et al. Gastroenterology. 2017 Jan. PMID: 27713038.