| Abstract |
Breast cancer is one of the two most common types of cancer affecting women in the developed world. The etiology of breast cancer is multifactorial, and the most important predisposing factors are family history, hormonal exposure, radiation exposure, benign hyperplastic breast lesions, previous history of breast cancer, alcohol intake, and animal fat intake. Breast cancer manifests with hyperplastic ductal or epithelial lobular growth, with gradual development of genetic alterations (including those concerning oncogenes and tumor suppressor genes) leading to monoclonal development of gradually malignant cells. The participation of specific genes in breast cancer, together with the effort to discover their exact role, is of great interest because of the diseases high incidence. In the present study, the implication of tumor suppressor genes ATM and p53 along with the oncogene H-ras was investigated in biopsies from women with sporadic breast cancer. The tumor suppressor gene ATM is a recently cloned gene. It is located in 11q23.1, and is often implicated in the development of the Ataxia-Telangiectasia syndrome and sporadic breast cancer. ATM heterozygous gene carriers bear a greater risk of developing breast cancer. In the lesions examined, ATM heterozygosity was elevated in sporadic breast cancer and could represent a potential risk factor for tumorigenesis in the breast. H-ras is a member of the ras family of genes, codes for P21, and its activation has been reported to be correlated with breast carcinogenesis. The first intron of H-ras gene (HRM) possesses a polymorphic site near the 5 end of the gene. Alleles P1, P2, and P3 contain 4, 2 and 3 repetitions of a single hexanucleotide region respectively. Moreover, H-ras bears a minisatellite VTR, at the 3 end of the gene, which displays linkage disequilibrium with HRM. There was a significant overrepresentation of P1 in the investigated breast cancer lesions. Our results possibly indicate that P1 homozygosity may represent a potential risk factor for breast carcinogenesis. Alterations of the VTR minisatellite at the 3 end of the H-ras gene were detected. In a single case, a shift in the mobility of the VTR alleles was observed after comparison of the amplification patterns of VTR between normal and breast cancer tissue. P53 gene is polymorphic at amino acid 72 of its encoding protein, resulting in an arginine or proline amino acid residue. It is suggested that p53 Arg homozygosity could represent a risk factor for patients with breast cancer lesions. The results of p53 polymorphism distribution were correlated with clinicopathological parameters of the patients, but no statistical correlation was observed. In the present study, there was an overrepresentation of homozygous p53 Arg compared to heterozygous or homozygous Pro alleles. In conclusion, detection of multiple alterations in these genetic loci may be an important step in the early diagnosis of breast cancer, while interactions with other factors can not be excluded.
|
Μελέτη γενετικών τόπων υπεύθυνων για τη λειτουργία των γονιδίων H-ras, p53 και ATM στον καρκίνο του μαστού
