Transforming growth factor Beta leucine10 proline variation and breast cancer risk in Iranian women.

Dear Editor in ChiefBreast cancer is one of the most frequent cancers around the world and in Iran. Both genetic and environmental factors have an important role in the developing of this disease. Transforming growth factor beta (TGF- β) protein is one of the genetic factors for breast cancer (1). It is a multi-functional cytokine found in almost all human tissue cells and regulates cellular processes such as cell division, differentiation, death, adhesion, and motility (2). In normal cells, TGF- β might act mainly as a tumor suppressor and inhibits cellular proliferation or promote cellular differentiation and apoptosis. TGF-s1 inhibits the proliferation of carcinomas in early stages of breast cancer (1). As cancer cells progress, regulatory mechanism of this protein becomes more complex because of changes in TGF-s1 expression and loss of negative cell signaling. Consequently, the more tumors advance, the more TGF-s1 express, which can be associated with phenotype and impaired clinical feature of this disease (3). Therefore, defining TGF-s molecular mechanisms and its involvement in the process of carcinogenesis is a major challenge.The TGF- s 1 gene is located on chromosome 19q13 and linkage studies and genetic models show that TGF-s Polymorphisms have relation with risk of developing breast cancer. Common variants of TGF-s1 gene may affect the production, secretion, or activity of this cytokine. Five different TGF-s1gene polymorphisms have been studied regarding breast cancer susceptibility (4). Polymorphism at codon 10(T29C) that result to Leu10Pro substitution in the signal peptide is most extensively studied polymorphism in the TGF-s1gene (5). C allele of T29C is associated with increased TGF- s1 serum levels, the result of association between this polymorphism and this disease is inconsistent in different populations. In Caucasian women, T allele of the T29C polymorphism was associated with increased risk of breast cancer (6). In contrast, in Korean and European population woman carrying C allele are more susceptible to breast cancer (7). Some studies also show no association between this polymorphism and breast cancer. According to these results, we investigated whether TGFβ1 gene polymorphism in codon 10 is associated with Breast cancer in Iranian population.This study as a case-control was performed between 60 women patients who had suffering from breast cancer attending Different hospitals of Yazd (central part of Iran) during the period from February 2012 - October 2014 and 60 healthy controls. Patient mean age was 51.2 years. The control did not have any history of cancer and other disease with known genetic predisposition. The study was confirmed by the local Ethics Committee of our center and all cases participated in this study voluntarily. Genomic DNA of the samples was extracted according to Saremi et al. protocol and the isolated DNA was quantified by the nanodrop and agarose gel (8). Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) was applied for detection of the polymorphisms of TGF-b1 gene at codon 10 (T29C) (rs1982073). We used target DNA, allele specific ARMS primer, and the common primer in two separate complimentary reactions for each allele. By this means, homozygote or heterozygote individuals for this mutation can be detected (9). Primers for detection of this polymorphism were Sense (common) primer 5'gttgtgggtttccaccattag-3', Antisense (ARMS) C-primer (pro 10 allele) 5'-ctccgggctgcggctgctgcC-3', Antisense (ARMS) T-primer (Leu 10 allele) 5'ctccgggctgcggctgctgcT-3'. These primers amplify 346 bp fragment that includes our polymorphism. We used internal primers (F5'-TGCCCTGTGCAGCTGTGGGTTGATT3'; R5'-GCCCCAGCTGCTCACCATCGCTATC3') amplifying a limited region of p53 gene located at chromosome 17p13.1, present in all samples as a positive control (10). Negative control was also applied for checking DNA contamination. Each Polymerase chain reaction contain 100 ng DNA, 10 mM TrisHCl, pH 8. …