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 recessive hereditary breast cancer.
Summary of Case-Control Data: 0 point To date, this gene-disease relationship has been studied in one large case-control study at the aggregate variant level in 2017 (PMID: 35172496). This study screened breast cancer cases from commercial laboratories and did not find significant association of biallelic variants in MUTYH with breast cancer.
Overall Summary: In summary, given that the only one case-control study showed no increased risk for breast cancer in biallelic 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 recessive hereditary breast cancer.
This gene-disease pair was originally evaluated as no known disease relationship by the Breast/Ovarian Cancer GCEP on 05/24/2017. 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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