Testing for Familial BRCA1–2 Mutations

Implications for Genetic Counseling and Risk Assessment

Abstract

INTRODUCTION: 

Genetic testing for hereditary breast and ovarian cancer increases as more individuals become aware of their risk. This has led to the identification of known familial mutations that allow for more facile assessment of mutation status. BRCA1 and BRCA2 are autosomal genes and thus equally likely to be inherited from either parent; accordingly, mutations should be equally distributed between maternal and paternal families. We evaluated individuals presenting for single-site testing to determine parental etiology of familial mutations.

METHODS: 

From 2008 through September 2013, 116 individuals underwent BRCA1–2 single-site testing at our center. All individuals underwent genetic counseling before testing and deleterious genes were identified and confirmed by written laboratory reports of a family member.

RESULTS: 

Of the 116 individuals presenting for single-site testing, pedigree analyses were not found in six women and one case was found to be a repeat analysis. Parental inheritance could not be determined in 12 patients; an affected sister or daughter was associated with all of these 12 patients. Of the remaining 97 individuals, 16 (16.5%) were identified as result of paternal inheritance, whereas 81 (83.5%) were evaluated because of maternally inheritance.

CONCLUSION: 

Our findings show a disproportionate ratio of maternal BRCA1–2 single-site mutations. This is most likely the result of the BRCA1–2 mutation phenotype to be more readily identified in women than men. However, this disparity highlights the need for physicians to intensify their efforts to obtain accurate family histories with a special effort to assess cancer history from one's paternal family.