Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast carcinoma.

Stromal cell-Derived Factor-1 (SDF-1, CXCL12) is one the ELR- CXC angiogenic chemokines. It contributes to hematopoiesis and lymphocyte trafficking. SDF-1 and its exclusive receptor, CXCR4, are reported to play important roles in tumor growth, angiogenesis and metastasis of different types of tumors such as breast, lung, prostate and pancreatic cancers. SDF-1 gene polymorphism, known as SDF1-3'A, has been investigated in HIV-1 infection and the incidence of breast cancer. This investigation was aimed to study the frequency of SDF1-3'A mutation in Iranian women with breast cancer. Results showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. Thus AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian women to breast cancer.

Analysis of BRCA1 and BRCA2 mutations in southern Iranian Breast cancer patients.

The germline mutations of breast cancer susceptibility genes 1 (BRCA1) and breast cancer susceptibility genes 1 (BRCA2) have been associated with a significant increase in breast cancer risk and certain other cancers. Among the most known mutations in these tumor suppressor genes are 5382insC and 185delAG in BRCA1 and 6174delT in BRCA2. The aim of the current study was to investigate the frequency of these BRCA1 and BRCA2 mutations in southern Iranian familial and sporadic cases with breast cancer.Two hundred fifty women with sporadic breast cancer, 55 women with a familial history of breast cancer in their first degree-relatives and 200 healthy women formed the studied groups. DNA from peripheral blood mononuclear cells was extracted and analyzed by a multiplex polymerase chain reaction method. The data of this investigation indicated that the aforementioned founder mutations were not detected in the groups studied. Our results indicate that 5382insC and 185delAG mutations in BRCA1 and 6174delT in BRCA2 have much less frequency in Iranian breast cancer patients.

Cytotoxic T lymphocyte antigen-4 gene in breast cancer.

The exon 1 polymorphism (49A/G) of ctla-4 gene corresponds to an amino acid exchange (threonine to alanine) in the leader peptide of the expressed protein. There are reports concerning the higher level of G allele in subjects with various autoimmune diseases, which has resulted in the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders. This study was undertaken to investigate the correlation of exon 1 (49A/G) polymorphism in the ctla-4 gene and breast cancer. The ctla-4 49A/G polymorphism was studied in 197 women with primary breast cancer and 151 age/sex matched normal individuals. The results indicated a significant difference between frequency of ctla-4 genotypes in patients and controls. The frequency of GG genotype was significantly decreased in breast cancer patients compared to controls (4.6% v.s. 12.6%, P = 0.012). There was also a significant positive correlation between tumor size and the existence of AA genotype in patients (P = 0.016). In addition, a positive correlation between AA genotype and lymph node involvement was observed (P = 0.042). The observed decrease in the frequency of GG genotype in the breast cancer patients is contrary to the frequently reported increase of GG genotype in autoimmune diseases. In addition, the data implies that polymorphism of ctla-4 exon 1 contributes in tumor progression.