BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity

• Published in: Medical oncology (Northwood, London, England) Vol. 29; no. 5; pp. 3272 - 3281
• Main Authors: Juwle, Abida, Saranath, Dhananjaya
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2012; Springer Nature B.V
• Subjects: Adult; Age of Onset; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; DNA Mutational Analysis; Female; Genes, BRCA1; Genes, BRCA2; Haplotypes; Hematology; Humans; India - epidemiology; Internal Medicine; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original Paper; Pathology; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction; India; SNPs; Mutations; Indian patients; Early-onset/sporadic breast cancer; Haplotype
• DOI: 10.1007/s12032-012-0294-9
• ISSN: 1357-0560; 1559-131X

We examined BRCA1/2 mutations and single nucleotide polymorphisms (SNPs) for identification of BRCA1 haplotypes, in early-onset breast cancer patients and their relatives, sporadic breast cancer patients, and unrelated normal healthy females, of Indian ethnicity. Peripheral blood DNA was amplified by polymerase chain reaction, at BRCA1/2 coding exons and subject to nucleotide sequencing using ABI 3100 Genetic Analyzer. We observed BRCA1/BRCA2 mutations in 52 % early-onset breast cancer patients and in 57 % relatives. Deleterious mutations detected in early-onset patients and relatives were 187delAG, 632insT, 1052delT, Q759X, Q780X, R1203X, 5154delC, IVS14 + 1G > A, IVS17 + 1G > T, and 632insT in BRCA1 gene; and 4075delGT, 5076delAA, 6079delAGTT, and W3127X in BRCA2 gene. A high degree of penetrance of BRCA1/2 gene mutations was observed in the relatives. BRCA1/2 SNPs were identified in the Indian population, and association of BRCA1 haplotypes with breast cancer was investigated. A significantly increased frequency of the SNPs 203G/A, 3624A/G and 7470A/G SNPs in BRCA2 gene was observed in normal controls indicative of a protective effect of the SNPs. BRCA1 haplotype 2 was most frequently observed in our population. Our study indicates a high incidence of BRCA1/BRCA2 gene mutations in the Indian patients. The BRCA1/2 mutations and SNPs are detailed on our website http://relibrca.rellife.com .