Abstract P6-08-31: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) as a cancer susceptibility gene
Authors: Singal Mukul , Godbole Manasi M , Povenzano Kim , Elmore Beth , Patel Mehul P 
Published: March 2020

Abstract
Background: Breast cancer is the most common cancer as well as the most common cause of cancer associated deaths in women worldwide. National Comprehensive Cancer Network has detailed criteria for identifying patients at risk for hereditary breast and ovarian cancer syndromes. Many multigene genetic testing panels are in use for screening and prognostication purposes. While pathogenic mutation in BRCA 1 and 2 mutations have been established as risk factors for developing breast cancer, the association of other germ line mutations with breast cancer is less defined. BRCA1 interacting protein C-terminal helicase 1 (BRIP1) influences the DNA repair ability as well as tumor suppressor function of BRCA1 and is associated with increased risk of ovarian cancer. Studies looking at association of BRIP1 mutation with risk of breast cancer have provided conflicting data and currently, BRIP1 is not implicated in causing breast cancer.
Methods: We conducted chart review of patients who were referred for genetic testing at the Lipson Cancer Institute/Rochester General Hospital, Rochester, NY and tested positive for BRIP1 mutation alone. Samples were sent to Myriad Genetics for Integrated BRACAnalysis® testing with myRisk® panel looking at 35 genes for mutation. BRIP1 mutations with abnormal protein production and/or function thought to increase risk for ovarian cancer (pathogenic or likely pathogenic) are reported as clinically significant. BRIP1 mutations with currently insufficient data to determine an increased risk are reported as variations of uncertain significance. The panel does not report benign and likely benign mutations.
Results: We found nine patients who tested positive for BRIP1 mutation and were negative for other genomic alteration including BRCA1 and BRCA2 mutation (Table 1 and 2). Four patients carried the known high risk BRIP1 mutation and five carried BRIP1 mutations of undetermined significance. One of four patients with known high risk BRIP1 mutations had a personal history but no family history of breast cancer while the remaining three had a family history but no personal history of breast cancer. All five patients with BRIP1 mutations of uncertain significance had both personal and family history of breast cancer.
Conclusion: The known high risk BRIP1 mutations are probably not associated with increased risk of breast cancer. However, at least some of the BRIP1 mutations of uncertain significance are likely very significant and associated with increased risk of breast cancer. This association needs to be confirmed in a larger patient population.
Table 1: Carriers of BRIP1 variations of uncertain significanceSerial NumberAge at time of screeningPositive BRIP 1 mutation Personal history of breast cancerFamily history of breast cancerAncestry164BRIP1 mutation, c.817A&gt;GYesYesGerman/ Irish278BRIP1 mutation, c. 2220G&gt;TYesYesHolland344BRIP1 mutation, c3237T&gt;GYesYesAfrican430BRIP1 mutation, c.380-17T&gt;AYesYesIrish/ English/ German555BRIP1 mutation, c.139C&gt;GYesYesScottish
Table 2: Carriers of high risk BRIP1 mutationsSerial NumberAge at time of screeningPositive BRIP 1 mutation Personal history of breast cancerFamily history of breast cancerAncestry169BRIP1 mutation, c.2255_2256delYesNoItalian/ Hungarian263BRIP1 mutation, c548delNoYesFrench Canadian337BRIP1 mutation, c.1045G&gt;CNoYesDutch460BRIP1 mutation, c.2099T&gt;ANoYesUnknown
Citation Format: Mukul Singal, Manasi M Godbole, Kim Povenzano, Beth Elmore, Mehul P Patel. BRCA1 interacting protein C-terminal helicase 1 (BRIP1) as a cancer susceptibility gene [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-31.