Abstract

Background: The prevalence of mutation in BRCA1 genes alarmingly augmented threat of Breast carcinoma among women. The occurrence of BRCA1 gene mutation in India is heterogeneous and varies according to geographical origin. Previous investigations have relied on subjective methods of recording prevalence and familial association. The influence of specific mutation biomarkers which may explain the link between, age, metastases, clinicopathological markers and risk of breast cancer has not been investigated prospectively in Uttar Pradesh (Northern India). Methods: This study was carried out on patients (N=381) diagnosed with breast cancer and further categorized into three groups according to family history. In the present work, blood/tissue samples were collected and mutations were detected using a PCR-SSCP (Single-strand conformation polymorphism) technique followed by sequencing. Results: In the study, 12 sequence variants out of which, eleven novels were identified in exon 11 of BRCA1 gene. BRCA1 mutations were detected in 4.7% (18/381) patients. Mutations in BRCA1 genes were significantly associated with family history and these mutations were found to be strongly associated with metastatic presentation (P=0.042, OR=6.567, 95% CI=1.073-40.174), younger age (P=0.032, OR=11.244, 95% CI=1.227-103.062), and negatively correlated with ER/PR/HER2. Thus, this can serve as important milestone in diagnosis of familial breast cancer. Conclusion: The higher prevalence of BRCA1 mutation among North Indian Breast cancer patients was associated with family history, metastases and younger age. The only alternate apart from early diagnosis is opting for a routine breast screening, which will prove to be a viable option for prevention in carcinoma of breast & better survival.

Keywords: Breast cancer; Metastases; BRCA; Mutation; SSCP