Germline BRCA1 mutation and survival analysis in familial breast cancer patients in Kerala; South India.

Mutations in breast cancer susceptibility gene BRCA1 have been identified in breast or breast/ovarian cancer families from different ethnic background. We analyzed a total of 79 samples for BRCA1 mutation, using Conformation Sensitive Gel Electrophoresis (CSGE) followed by sequencing. The overall survival of BRCA1 mutation carriers was also investigated. BRCA1 mutation was detected in 11 out of the 29 (38%) patients. Four different alterations were detected of three which were novel. A missense mutation in exon 7, 465G>A was detected in 1 patient (9%). Another missense mutation 932 G>A was observed in three patients (27.3%) and a truncation mutation 1027delA, was observed in one patient (9%). The fourth type of mutation (185delAG) which also results in protein truncation was observed in 6 different patients (54.5%). Kaplan-Meier survival analysis revealed a median overall survival of 34 months for BRCA1 mutation positive breast cancer patients and 71 months for BRCA1 negative breast cancer patients. The median overall survival of BRCA1 truncation mutation carriers was 26 months. Our data showed high prevalence of BRCA1 gene mutation among breast or breast/ovarian cancer families in South India and breast cancer patients having BRCA1 mutations were associated with poor prognosis.