Browsing by Subject "Breast Cancer Genetic aspects."

Filter results by typing the first few letters
Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Identification of genes induced by BRCA1 in breast cancer cells
    (2002) Atalay, Arzu
    Inherited mutations of the BRCA1 gene predispose to cancer of the breast, ovaries and other organs. The BRCA1 protein product is implicated in the maintenance of chromosomal integrity as BRCA1-deficient cells display gross chromosomal rearrangements. Chromosomal instability in BRCA1-deficient cells is related to inappropriate DNA double-strand break repair. The role of the BRCA1 gene in the maintenance of chromosomal integrity is linked to a number of biological properties of its protein product including transcriptional regulation. The aim of this study is to identify genes that are regulated by BRCA1. Initial attempts to overexpress BRCA1 in breast cancer cells with the tightly-regulated ecdysone inducible system did not result in the desired levels of BRCA1 protein and ectopic BRCA1 expression was therefore performed by using the constitutive expression vector. In this study, we have identified genes whose expression levels are upregulated as a result of BRCA1 overexpression in MCF7 breast carcinoma cells by using the suppression subtractive hybridisation (SSH) method. Differential screening, sequencing and homology search studies showed that BRCA1 overexpression in breast cancer cells leads to transcriptional upregulation of distinct classes of genes encoding proteins involved in cellular processes such as DNA repair, chromosome assembly and segregation, signal transduction, RNA surveillance, ubiquitin-mediated proteolysis, amino acid transport, RNA metabolism and glucose metabolism. This study is the first to report BRCA1- induced genes in breast carcinoma cells with the SSH technique. The identified genes in this study may provide new insights into the tumour suppressor functions of BRCA1.
  • Thumbnail Image
    ItemOpen Access
    Polymorphisms in P21 (CODON 31) and P53 (CODON 72) : association with breast cancer susceptibility in the Turkish and Greek populations
    (2003) Çolakoğlu, Gülsen
    The aim of this study was to investigate the potential association of p53 codon 72 and/or p21 codon 31 polymorphisms with increased susceptibility for breast cancer either independently or combined in the Turkish and Greek populations. A case-control study was conducted for both populations and the genotypes of the subjects were determined by PCR-RFLP (Turkish; p53 genotypes for 274 cases and 221 controls, p21 genotypes for 322 cases and 246 controls, Greek; p53 genotypes for 138 cases and 138 controls, p21 genotypes for 156 cases and 136 controls were obtained). Binary logistic regression was used to analyze the data. Although the Greek study population alone did not give statistically significant results, the p53 codon 72 Arg/Arg inheritance was found to be significantly associated with breast cancer susceptibility in the Turkish study population (OR=2.16; 95% CI=1.08-4.31) as well as in the combined population of Turkish and Greek subjects (OR=2.35; 95% CI=1.25-4.41). This association was further increased with increased BMI (OR=3.86; 95% CI=1.12-13.26) in the Turkish population but the result should be treated with caution because of the wide confidence interval. The inheritance of the combined p21 codon 31 Arg/Arg or Ser/Arg genotypes increased breast cancer susceptibility in the Turkish study population (OR=1.15; 95% CI=0.75-1.76) although the result is not statistically significant. The most prominent result of this study is that there is an interaction between the p53 Arg72Arg and p21 Arg31Arg or Ser31Arg genotypes for breast cancer susceptibility (OR=2.66; 95% CI=1.06- 6.66). These results let us to conclude that there is a strong association between the p53 Arg72Arg genotype and breast cancer risk in the Turkish population and that the combination of high-risk allelic variants of both p53 and its downstream effector protein p21 may have a role as a risk factor for breast cancer development.
  • Thumbnail Image
    ItemOpen Access
    Polymorphisms of Glutathione S- transferase genes (GSTM1, GSTP1, and GSTT1) and breast cancer susceptibility in the Turkish population
    (2002) Demir, Ebru
    The potential association between the Glutathione S- transferase genes GSTM1, GSTT1, GSTP1 and breast cancer susceptibility was investigated in a case control study of 264 female patients and 233 age-matched controls in the Turkish population. The combined GSTP1 105 Ile/Val or Val/Val genotypes was significantly associated with breast cancer risk in all women (odds ratio OR=1.64, 95% confidence interval CI=1.09-2.47 and in premenopausal women is OR= 2.01, 95% CI=1.06-3.83). Neither GSTM1 nor GSTT1 was found to be associated with breast cancer. Distribution of GSTP1 genotypes was stratified according to body mass index (BMI), age, age at menarche, age at full-term pregnancy, number of fullterm pregnancies, and family history of breast cancer. The association of the combined GSTP1 105 Ile/Val or Val/Val genotypes with breast cancer risk was further exacerbated in women with high BMI (OR=2.12, 95% CI=1.35-3.62), but not with a low BMI (OR=0.78, 95% CI=0.45-1.34). These findings support the role for the combined GSTP1 105 Ile/Val or Val/Val genotypes in the development of breast cancer, particularly with a high BMI.