• Risk estimation
• Cancer genetics
• Gene panel testing
• ovarian cancer
• breast cancer

BRIP1 is one of several DNA damage response genes that have been implicated in both Fanconi Anaemia and hereditary breast and ovarian cancer. BRIP1 binds to the BRCT1 C-Terminus (BRCT) domain and functions in BRCA1-dependent DNA repair and cell cycle control.1 Biallelic mutations in BRIP1 cause Fanconi Anaemia type J.1 Heterozygous mutations in other Fanconi Anaemia genes such as BRCA1, BRCA2 and PALB2 are associated with an increased risk of breast cancer,2 so it is reasonable to consider BRIP1 as a candidate breast cancer susceptibility gene.

BRIP1 is currently included on most commercially available hereditary cancer gene panels, with both breast and ovarian cancers given as indication for testing. The basis for inclusion of BRIP1 as a breast cancer susceptibility gene is a single study of familial breast cancer3 (1212 cases and 2081 controls), in which the relative risk for breast cancer was estimated to be about twofold (p=0.012). Although published in 2006, the results of that study have never been confirmed, and the role of BRIP1 in contributing to breast cancer risk remains unclear.

In this issue of JMG, Easton and colleagues,4 using a very large series of cases and controls, report a failure to replicate the association3 between BRIP1 truncating mutations and breast cancer risk. Here, the authors first …