الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Background: Breast cancer is the most commonly diagnosed cancer in females worldwide, accounting for 25% of all female cancers. Metastasis is the main cause of breast cancer related mortality accounting for approximately 90% of breast cancer deaths. Metastasis-suppressor genes such as NME1 and KISS1 can inhibit cancer metastasis. BRCA1 and BRCA2 genes are two tumor suppressor genes. Their mutations in increase women’s risk of developing breast cancer. Objectives: To investigate the role of genetic polymorphisms of NME1 and KISS1 genes in prediction of patients who are genetically predisposed to the development of metastatic disease, and to study the frequency of association of mutations in BRCA1 and BRCA2 genes with breast cancer. Methods: Whole blood was obtained from all subjects of the study. DNA was isolated from blood samples. Genotyping of NME1 gene EcoR1 (rs34214448) polymorphism and KISS1 gene (rs5780218) polymorphisms was done by (PCR-RFLP). Detection of c.68_69delAG (185delAG) and c.5266dupC (5382insC) in BRCA1 gene and c.5946delT (6174delT) in BRCA2 gene was done by (ARMS -PCR). Results: A statistically significant association between NME1 EcoR1 (rs34214448) and KISS1 (rs5780218) polymorphisms and the risk of breast cancer was found. The homozygous wild (G/G) genotype of EcoRI polymorphism is associated with higher risk of breast cancer metastasis. In the breast cancer group, the BRCA2; c.5946delT (6174delT) mutation was the most frequent followed by BRCA1; c.68_69delAG (185delAG) mutation. The heterozygous mutant genotype of BRCA1 gene; c.5266dupC (5382insC) mutation and the homozygous wild genotype of BRCA2 gene; c.5946delT (6174delT) mutation are associated with aggressive disease behavior showing high risk of distant metastasis and advanced tumor stages. Conclusion: NME1 EcoR1 (rs34214448) and KISS1 (rs5780218) polymorphisms are associated with the risk of breast cancer. Detection of BRCA1 and BRCA2 gene mutations is helpful for early diagnosis and prognosis of breast cancer patients. Keywords: Breast cancer, Metastasis, NME1, KISS1, BRCA, Gene polymorphism, Mutation.