ORIGINAL PAPER BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity Abida Juwle • Dhananjaya Saranath Received: 31 May 2012 / Accepted: 19 June 2012 / Published online: 3 July 2012 Ó Springer Science+Business Media, LLC 2012 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 nucle- otide 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 hap- lotypes 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. Keywords BRCA1/2 Á Mutations Á SNPs Á Haplotype Á Indian patients Á Early-onset/sporadic breast cancer Introduction Breast cancer is the most common malignancy in women worldwide, with an incidence of 1.38 million cases con- tributing 22.9 % of the total cancer burden in women [1]. The incidence rates of breast vary in various geographic locales with North America and Europe considered high-risk areas, and Asia and Africa indicated as low-risk areas. India constitutes a low-risk region for breast cancer, with 115251 cases reported annually [1]. However, breast cancer is the most common female cancer in several urban areas of India including New Delhi, Mumbai, Ahmedabad, Pune, Nagpur, Trivandrum, and Karunagappally, and the second most fre- quent cancer in females in Chennai and Bangalore [2, 3]. Breast cancer is primarily seen in women at a later age of [ 50 years, and several risk factors have been associated with breast cancer [4, 5]. However, 5–12 % of breast cancers are early-onset cancers in women \ 45 years, associated with a genetic predisposition and inheritance of mutated dominant susceptibility genes including BRCA1/BRCA2 [6]. The mutated BRCA1/BRCA2 genes increase lifetime breast cancer risk to 85 % and ovarian cancer risk to 60 %, as compared to a 12 % lifetime risk of breast cancer and 1 % lifetime risk of ovarian cancer in women without mutations in BRCA1 and BRCA2 [7]. A compilation of 1500 BRCA1/ BRCA2 mutations comprising nonsense, missense, frame- shift mutations, and large and small deletions are recorded in Breast Cancer Information Core (BIC) database [8]. Specific BRCA1 and BRCA2 mutations have been associated with certain ethnic populations, and founder mutations identified in several groups. In the Ashkenazi Jewish population, three A. Juwle Á D. Saranath (&) Molecular Medicine, Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Thane Belapur Road, Rabale, Navi Mumbai 400701, India e-mail: saranathd@aol.com A. Juwle e-mail: abida_juwle@hotmail.com 123 Med Oncol (2012) 29:3272–3281 DOI 10.1007/s12032-012-0294-9