TEST:

23andMe PGS Genetic Health Risk Report for MUTYH-Associated Polyposis (MAP)

"23andMe Holding Co...today received FDA clearance for a genetic health risk report on a hereditary prostate cancer marker...This is the Company’s third cancer risk report clearance, following the FDA’s prior authorization for 23andMe’s BRCA1/BRCA2 (Selected Variants) Genetic Health Risk report and its clearance for MUTYH-Associated Polyposis (MAP), a hereditary colorectal cancer syndrome...These two reports along with the new Hereditary Prostate Cancer (HOXB13-Related) report have been included by the FDA in a single 'Cancer Predisposition Risk Assessment System' regulation...These three 23andMe reports are the only direct-to-consumer genetic health risk reports for inherited cancers that have been authorized by the FDA for use without prescription."

Patients with duodenal adenoma(s) ≥10 mm and ampullary adenomas of any size are suggested to be referred to an expert center for endoscopic therapy, particularly endoscopic mucosal resection and endoscopic ampullectomy. Nonetheless, despite the logic of this approach, the long-term efficacy of endoscopic therapy is still to be demonstrated.

Our study confirms that patients with Y179C biallelic mutation present a higher risk for colonic, gastric and duodenal polyps. These findings highlight the importance of genotype-phenotype correlation with potential implications in management of PAM patients. Also the elevated number of adenomas in the monoallelic carriers validates the surveillance proposed.

"Please refer to National Comprehensive Cancer Network (NCCN) clinical practice guidelines to determine an appropriate testing strategy and guide medical screening and management. This 2021 edition of the American College of Medical Genetics and Genomics (ACMG) technical standard supersedes the 2013 edition on this topic."

"The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function."

"The patient in this case had a first phenotype of thyroid cancer at age 44, which earlier 2 years than the alimentary system cancers. In conclusion, our case report creases the in-depth understanding of the MAP heterogeneous phenotype and further reminds recommendations for improvement of health management and genetic counseling, special treatment plans."

We report here the revised version of this work which successively considers the phenotype and the tumor risks associated with this genotype, the differential diagnoses, the indication criteria and the strategy of the molecular analysis and the recommendations for the management of affected individuals. We also discuss the phenotype and the tumor risks associated with mono-allelic pathogenic variants of MUTYH gene.