title: BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity.
abstract: 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 .
authors: Molecular Medicine, Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Thane Belapur Road, Rabale, Navi Mumbai, 400701, India. abida_juwle@hotmail.com
authors: Abida
authors: A
authors: Juwle
authors: Dhananjaya
authors: D
authors: Saranath
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction