Abstract P5-12-01: MUTYH In A Cancer Population
Authors: Smith Linda Ann 
Published: March 2023

Abstract
Background: Germline genetic testing has become a critical quality point in caring for breast cancer patients and high risk patients. Originally testing panels were extremely limited, but now expanded hereditary cancer testing panels are more common and have raised the question of other genes being linked to cancer risk. In this cohort, we examine the prevalence of the gene mutation MUTYH in a high risk population tested with expanded panels.
Method: Patient data was obtained from an IRB-approved multi-center longitudinal, observational study, in which 2276 patients underwent expanded (&gt;9 gene) germline genetic testing and also contributed personal and family history of cancer information. The average age in this cohort was 58.58 years old, with 2197 (96.53%) Female and 1762 (77.43%) with a personal cancer diagnosis and 1625 (71.40%) with a family history of cancer. Germline genetic tests were lab agnostic and tested an average of 73.2 genes (1214 or 53% tested with 85 gene panel) and a range of 9-85 genes tested.
Results: Overall, the patients had a 16.70% positivity rate for pathogenic germline result of genetic test, with 42 (1.85%) reporting a Monoallelic MUTYH pathogenic variant (PV) result. Of those reporting a MUTYH PV, the average age was 58.48, with 40 (95.24%) females and 35 (83.33%) with a personal cancer diagnosis and 32 (76.19%) with a family history of cancer. Those patients with and without a personal and family history of cancer were compared, and found that a personal history of cancer has a very significant difference in MUTYH PV rate (9.56e-6) while family history of cancer does not have a significant difference (0.496). In the patients with a MUTYH PV and a diagnosis of cancer, 31 (88.57%) had a breast cancer diagnosis and only 1 (2.86%) had a colorectal cancer diagnosis - 73.81% and 2.38% of all MUTYH carriers. Of the 32 patients who had information about their family cancer diagnoses, there were 27 patients with multiple diagnoses and only 5 with a single family diagnosis, with 116 total family members with reported diagnosis. There were 44 breast cancer diagnoses in 23 of the MUTYH PV carriers’ families, which is 71.88% of all patients with family cancer information and 54.76% of all MUTYH PV carriers. There were 6 colorectal cancer diagnoses in 6 of the MUTYH PV carriers’ families, which is 18.75% of all patients with family cancer information and 14.29% of all MUTYH PV carriers.
Conclusions: Our findings match with other reported cancer cohorts (on the order of 1-2%, Thompson et al). Monoallelic MUTYH has a significant association with both personal history of cancer. These findings suggest that patients with a personal and or family history of cancer should consider expanded gene panel testing which includes MUTYH.
Requested Data 7/13 - MUTYH carrier personal and family history of cancer
Citation Format: Linda Ann Smith. MUTYH In A Cancer Population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-01.