Novel Sequence Variants and a High Frequency of Recurrent Polymorphisms inBRCA1Gene in Breast Cancer Women of North Coastal Andhra Pradesh

Abstract

KEYWORDS Breast Cancer. Genetics. BRCA1. North Coastal Andhra Pradesh ABSTRACT Owing to its high incidence coupled with relatively good prognosis, breast cancer is the most prevalent cancer in the world today. Germ line mutations in the susceptibility gene BRCA1 in hereditary breast/ovarian cancer, though low in prevalence, are highly penetrant and show geographical variations. Most cancer-associated BRCA1 mutations identified to date result in the premature translational termination of the protein. However , the molecular and genetic effects of missense mutations remain largely unknown. There have been only a few reports from India on mutations in BRCA1 and none from North Coastal Andhra Pradesh. We have analyzed 114 breast cancer patients with (N = 9) and without (N = 105) a family history of breast cancer , 22 at risk relatives from familial (n=1 1), sporadic (n=11) cases and 97control subjects for mutations in exons 2 and 1 1 and their intron-exon boundaries of BRCA1 gene by direct sequencing. Sequence alignment was carried by CLUST AL W and PSI-BLAST. Out of eight sequence variants found, one novel deleterious frame-shift mutation (c.2717insA), one novel polymorphism (c.1400A>G), five previously reported common polymorphisms in exon 11 and one intronic (intron 1) variant (base1822C>T) were observed. All the identified polymorphisms in exon 11 fall in DNA binding domain of BRCA1 protein.