MUTYH is a DNA glycosylase involved in the base excision DNA repair pathway. Biallelic and monoallelic variants in MUTYH were linked to multiple types of cancer and/or tumor, including hereditary breast cancer, familial ovarian cancer, familial adenomatous polyposis and colorectal cancer. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we have split these associations into different curations due to phenotypic differences and/or inheritance mechanism . Therefore, this curation solely focuses on autosomal dominant familial ovarian cancer.
Summary of Case-Control Data: 0 point To date, this gene-disease relationship has been studied in one cohort studies at the aggregate variant level. This cohort studies suggested no increased risk for ovarian cancer in monoallelic MUTYH variant carriers compared to controls (PMID: 27194394).
Overall Summary In summary, given that the only one cohort study showed no increased risk for ovarian cancer in monoallelic MUTYH variant carriers, and no experimental data support this gene-disease relationship, the Hereditary Cancer GCEP has disputed this gene-disease association. More evidence is needed to either support or entirely refute the role MUTYH plays in autosomal dominant ovarian cancer.
This gene-disease pair was originally evaluated as limited by the Breast/Ovarian Cancer GCEP on 11/29/2017. This re-curation was approved by the ClinGen Hereditary Diseases GCEP on 06/23/2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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