Novel sequence variants and a high frequency of recurrent polymorphisms in BRCA1 gene in Sri Lankan breast cancer patients and at risk individuals

A total of 130 patients with (N = 66) and without (N = 64) a family history of breast cancer, 70 unaffected individuals with a family history of breast cancer and 40 control subjects were analysed for BRCA1 mutations. All but exon 11 were screened by single strand conformation analysis (SSCP) and heteroduplex analysis. PCR products which showed abnormal patterns in SSCP were sequenced. Exon 11 was directly sequenced.Nineteen sequence variants were found in BRCA1 gene. Two novel deleterious frame-shift mutations; c.3086delT/exon11 (in one patient) and c.5404delG/exon21 (in one patient and two of her family members) were identified. A possibly pathogenic novel missense mutation (c.856T>G/exon 11) and three novel intronic variants (IVS7+36C>T, IVS7+41C>T, IVS7+49del15) were characterised. Ten previously reported common polymorphisms and three previously reported intronic variants were also observed.After screening of 66 patients with family history and 64 sporadic breast cancer patients, 2 deleterious mutations (c.3086delT and c.5404delG) in two families were identified and two more possibly pathogenic mutations (c.856T>G and IVS17-2A>T) in two families were identified.BRCA1 - Gene Bank: Accession # U14680 Version # 14680.1Breast Cancer is the commonest malignancy in women worldwide, accounting for 23% of all cancers and is surpassed only by lung cancer when cancers of both genders are considered [1]. In Sri Lanka, breast cancer is the most commonly diagnosed cancer among women, currently accounting for 25% of cases. However, Sri Lanka has a lower age standardized incidence rate of breast cancer (18.25) compared to other Asian countries (range 18.7 to 33.3) and to North America (99.4) [1,2].A number of risk factors are known to affect the likelihood of developing breast cancer. Among them most potent are the inherited mutations in the breast cancer susceptibility (BRCA) gene 1 and 2 [3]. BRCA1 and BRCA2 mutations are highly penetrant with a lifetime risk of 46–87% and