'Ovarian Cancer(yumurtalık kanseri)' kategorisi icin arsiv

Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients.

Yazan: admin Tarih: Oca 25th, 2011 | Kategori:: BRCA1, BRCA2, Breast cancer(Göğüs kanseri), Ovarian Cancer(yumurtalık kanseri), Prostate cancer(Prostat Kanseri)

Cancer Genet Cytogenet. 2010 Dec;203(2):230-7.

Manguoğlu E, Güran S, Yamaç D, Colak T, Simşek M, Baykara M, Akaydın M, Lüleci G.

Faculty of Medicine, Department of Medical Biology and Genetics, Akdeniz University, Antalya 07070, Turkey. emanguoglu@akdeniz.edu.tr

Abstract

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.


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An investigation of relationships between hypoxia-inducible factor-1 alpha gene polymorphisms and ovarian, cervical and endometrial cancers.

Yazan: admin Tarih: Ağu 3rd, 2008 | Kategori:: Cervical cancer, Endometrial cancers, Ovarian Cancer(yumurtalık kanseri)
Cancer Detect Prev. 2007;31(2):102-9. Epub 2007 Apr 6.

Konac E, Onen HI, Metindir J, Alp E, Biri AA, Ekmekci A.

Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.

BACKGROUND: DNA sequence variations in HIF-1 alpha gene might yield changes both in the production outcomes and in the activities of the gene. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. In this study, we aimed to determine how the three single nucleotide polymorphisms (SNPs, C1772T and G1790A exon 12, C111A exon 2) in the HIF-1 alpha gene coding regions affect the ovarian, cervical and endometrial cancer patients in the Turkish population. A study on this relationship has not been conducted to date. METHOD: 102 gynecologic cancer patients and 107 healthy controls were studied. Genotypes of the three polymorphisms were analyzed by PCR-RFLP. RESULTS: There was no significant difference between ovarian cancer patients and controls in terms of the distribution of C1772T genotypes and alleles (P>0.05). However, there was a highly significant increase in the frequency of both CT 1772 and TT 1772 genotypes in patients with cervical and endometrial cancers compared with healthy controls. In fact, 1772T allele-carriers (CT+TT genotypes) showed an association with the risk of cervical and endometrial cancers compared to the wild type (OR=3.84, 95% CI: 1.65-8.93; OR=7.41, 95% CI: 2.33-23.59, respectively). C1772T polymorphism was not associated with family history concerning gynecologic and/or other cancer types, stages (I-IV) and grades of tumor, smoking habits and existence of other diseases that generate a hypoxic microenvironment even after multivariable logistic regression analysis. As for HIF-1 alpha G1790A genotypes, the frequencies of G alleles were 98% in ovarian patients and 100% in the control group. We found no significant difference in the genotype distribution and allele frequencies between the ovarian patients and healthy control subjects. There were no GA and AA genotypes among the cervical and endometrial cancer patients. As for HIF-1 alpha C111A polymorphism, we did not find CA and AA variants of the gene in controls or in any of the three types of patients. CONCLUSION: Our results suggest that the C1772T polymorphism of the HIF-1 alpha may be associated with cervical and endometrial cancers.


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Lack of association between -460 C/T and 936 C/T of the vascular endothelial growth factor and angiopoietin-2 exon 4 G/A polymorphisms and ovarian, cervical, and endometrial cancers.

Yazan: admin Tarih: Ağu 3rd, 2008 | Kategori:: Cervical cancer, Endometrial cancers, Ovarian Cancer(yumurtalık kanseri), Uterine Cancer(Rahim kanseri)

DNA Cell Biol. 2007 Jul;26(7):453-63.

Konac E, Onen HI, Metindir J, Alp E, Biri AA, Ekmekci A.

Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey. ecemercanoglu@yahoo.com

Tumor growth, which employs a number of regulators, requires the formation of new blood vessels. The most important regulators are vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). DNA sequence variations in VEGF and ANGPT-2 genes may lead to altered productions and/or activities of these genes. In this study, we aimed to determine the polymorphic effects of the changes in the VEGF -460 C/T, VEGF 936 C/T, and ANGPT-2 exon 4 G/A, which we perceive as risk factors in the progress and metastasis of cancer, on the gynecologic cancer patients in the Turkish population. Forty-seven ovarian, 32 cervical, and 21 endometrial cancer patients and 106 healthy controls were studied. The genomic DNA was extracted from the whole blood by using DNA extraction techniques. DNA samples were analyzed by polymerase chain reaction and restriction fragment length polymorphism. There were no significant differences between any of the three types of gynecologic cancer patients and controls in terms of the distribution of VEGF -460, VEGF 936, and ANGPT-2 genotypes and alleles (p > 0.05). Odds ratios (ORs) were calculated by logistic regression analysis in comparison with the most common homozygote genotype observed in the studied population. No evidence of a relationship that would constitute a risk factor (p > 0.05) was found between genotype and allele frequencies of patients and controls for VEGF -460, VEGF 936, and ANGPT-2 genes. A multivariable logistic regression analysis with the involvement of covariant factors, such as the history of gynecologic cancer and/or other cancer types in the family, stages of tumor, smoking habits, and existence of other diseases, did not change the results. The present study is the first case-control study of VEGF and ANGPT-2 polymorphisms in relation to ovarian, cervical, and endometrial cancers.


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