A study of The Frequency and Type of Mutation in Exon 11 in BRCA1 and BRCA2 Genes In Breast Cancer Women With Positive Family History

Abstract

Background:Both BRCA1 and BRCA2 are tumor suppressor gene and are inherited as an autosomal dominant. The cumulative lifetime risk of developing invasive breast cancer for those with BRCA1 or BRCA2 mutations ranges from 53% to 89%. Familial breast cancer represent less than 10% of all cancers of the breast, and cancers related to BRCA1 and BRCA2 familial disease account only for three-fourths to two-thirds of these cases. In women younger than 35 year old with CA breast, 10% to 15% have a BRCA1 mutation. Females with mutations involving BRCA 1/2 who are already affected by breast cancer have an increased risk of breast cancer involving the other breast of 52% and 66%. Objective: To identify the frequency and the type of mutation in exon 11 in the genes BRCA1 and BRCA2 in breast cancer women with positive family history. Patients and Methods: This is a prospective study of fourteen females having breast cancer with positive family history of breast cancer. The study done in Baquba Teaching Hospital over a period of eight months (October 2016-July 2017). The age range of the patients was 40-70 years. Genomic DNA was extracted from lymphocytes yielded from the peripheral blood using the salting out procedure. Primers were used to amplify exon 11 region of the genes BRCA1 and BRCA2 by using polymerase chain reaction (PCR) cycling. Results: A total of eight variants in the BRCA1 gene and four variants in the BRCA2 gene were seen. Only one deleterious germline mutation in BRCA1 was detected in 1/14 (7.14%). The patient with deleterious mutation was 31 year-old and was having strong family history of the disease (two relatives, first and second degree). The sequence variant of the mutation was c.795_789delTT with an effect as p.Val256-Ser261ValLys. The remaining 11 identified variants belonging to BRCA1 and BRCA2) are classified as polymorphisms or unknown variants. Conclusion:BRCA1 and BRCA2 mutations in females with breast cancer with positive family history of the disease is never low and cannot be neglected. Therefore screening for these mutations is important for strict follow up of those with positive results.

Keywords

• Breast cancer, BRCA 1, BRCA2.