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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Genetic Variations in the Hypoxia-inducible Factor-1{alpha} Gene and Lung Cancer.

Yazan: admin Tarih: Ağu 24th, 2009 | Kategori:: Cancer (Kanser), Gene polymorphisms, Lung cancer (Akciğer Kanseri), polymorphisms

Exp Biol Med (Maywood). 2009 Jun 22.

Konac E, Dogan I, Onen IH, Yurdakul AS, Ozturk C, Varol A, Ekmekci A.

Gazi University, Faculty of Medicine.

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alpha gene may cause changes in the activity of the protein which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alpha polymorphisms [C>T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeat in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alpha polymorphisms (P>0.05). No significant relationship was found between the C>T substitution in intron 8 and P582S haplotypes and development of lung cancer. Also, no significant difference was observed between the genotypes and clinopathological characteristics of the cases. These findings showed that polymorphisms of the HIF-1alpha gene did not confer susceptibility to lung cancer.


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Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population.

Yazan: admin Tarih: Ara 5th, 2008 | Kategori:: Thyroid cancer(Tiroid kanseri)

 

J Endocrinol Invest. 2008 Sep;31(9):750-4.

Erdogan M, Karadeniz M, Ozbek M, Ozgen AG, Berdeli A.

Department of Endocrinology and Metabolism Disease, Ege University Medical School, Bornova, Izmir, Turkey. drmerdogan61@yahoo.com

OBJECTIVE: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. RESULTS: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). CONCLUSIONS: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.


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Association of Genetic Polymorphisms in Vitamin D Receptor Gene and Susceptibility to Sporadic Prostate Cancer.

Yazan: admin Tarih: Kas 11th, 2008 | Kategori:: Prostate cancer(Prostat Kanseri)

Exp Biol Med (Maywood). 2008 Oct 10. [Epub ahead of print]

Onen IH, Ekmekci A, Eroglu M, Konac E, Yesil S, Biri H.

Gazi University, Faculty of Medicine.

Genetic and environmental factors are involved in Prostate Cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and one hundred and fifty-seven age-matched healthy controls were genotyped for the ApaI (rs7975232), BsmI (rs1544410) and TaqI (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the ApaI polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and ApaI “a” allele carriers (Aa+aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the ApaI polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the BsmI and TaqI polymorphisms were similar between cases and controls (P >0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P >0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish Population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa.


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