Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population.

Yazan: admin Tarih: Oca 25th, 2011 | Kategori:: CYP1B1, N-acetyltransferase

Anticancer Res. 2010 Jul;30(7):2885-9.

Ozbek YK, Oztürk T, Tüzüner BM, Calay Z, Ilvan S, Seyhan FM, Kisakesen HI, Oztürk O, Isbir T.

Department of Molecular Medicine, Institute of Experimental Medicine (DETAE), Istanbul University, Vakif Gureba Cad Sehremini, Istanbul, Turkey.

Abstract

BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated.

PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Results and

CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004).


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Vitamin D receptor gene polymorphisms in breast cancer.

Yazan: admin Tarih: Ağu 10th, 2008 | Kategori:: Breast cancer(Göğüs kanseri)

Exp Mol Med. 2003 Dec 31;35(6):550-5.

Buyru N, Tezol A, Yosunkaya-Fenerci E, Dalay N.

Cerrahpasa Medical Faculty, Department of Medical Biology, Istanbul University, Istanbul, Turkey.

Breast cancer is the leading cause of cancer death among women around the world and its incidence is annually increasing. The vitamin D receptor (VDR) gene is a member of the nuclear receptor superfamily, which is expressed in breast tissue and known to modulate the rate of cell proliferation. Association between the VDR gene polymorphisms and cancer development has been suggested by several studies. However, the relationship between VDR polymorphisms and breast cancer is controversial and has not been confirmed by all studies. The purpose of this study was to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polymorphisms with breast cancer in Turkish patients. In this study, 78 patients with breast cancer and 27 healthy individuals were enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients with breast cancer was similar to that in the normal population. Our data indicate that no significant differences exist between the patients and control subjects.


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Homozygosity at the C677T of the MTHFR gene is associated with increased breast cancer risk in the Turkish population.

Yazan: admin Tarih: Ağu 8th, 2008 | Kategori:: Breast cancer(Göğüs kanseri), Gene polymorphisms

n Vivo. 2005 Sep-Oct;19(5):889-93.

Deligezer U, Akisik EE, Dalay N.

Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.

BACKGROUND: Folate deficiency is implicated in cancer development. Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene can modulate the effect of folate. In this case-controlled study, a possible effect of the common MTHFR C677T (ala–>val) polymorphism on breast cancer susceptibility in Turkish patients was investigated. MATERIALS AND METHODS: Polymorphism analysis was performed by melting curve analysis. RESULTS: The variant allele valine (677T) was more frequent among the patients (30.1%) than in controls (23.9%). This difference was weakly significant (p = 0.046; OR = 1.37) and due to a significantly higher frequency of the valine homozygotes (677TT) among the patients (12.1% vs. 5.4%; p = 0.013, OR = 2.5). Among the patients diagnosed at more than 40 years of age, a more pronounced association of the valine homozygotes with breast cancer risk was observed (p = 0.009; OR = 3.3). CONCLUSION: Homozygosity for the low-activity C677T genotype (TT) may represent a genetic determinant increasing breast cancer risk.


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p53 genotypes and haplotypes associated with risk of breast cancer.

Yazan: admin Tarih: Ağu 3rd, 2008 | Kategori:: Breast cancer(Göğüs kanseri)
Cancer Detect Prev. 2007;31(3):207-13. Epub 2007 Jun 18.

Buyru N, Altinisik J, Demokan S, Dalay N.

Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

INTRODUCTION: The biological significance of sequence variants in form of SNPs needs to be carefully evaluated, as conflicting associations with cancer predisposition have been reported. Haplotypes, the combination of closely linked alleles on a chromosome, play key roles in the study of the genetic basis of disease. There is strong evidence that different polymorphisms within a single gene in cis position can interact to create a large effect on the observed phenotype. Several polymorphisms have been reported in the p53 gene. Some of these are within the coding region and may affect the function of the p53 protein, others are within introns or non-coding regions, and their significance is unclear. In this study, we investigated the association of specific p53 genotypes and haplotypes with risk of breast cancer. METHODS: One hundred and fifteen patients with breast cancer and 63 healthy individuals were analyzed. DNA was isolated by salting out. The polymorphic sites were analyzed by PCR RFLP. Pearson’s chi(2) and Kolmogorof Simirnow tests were used for statistical analyses. Extended haplotype frequencies were estimated. RESULTS: The distribution of the genotypes was similar for all three polymorphisms in the cases and the controls. Our estimated haplotype results indicate that the intron 3 (+16bp)|exon 4 (Arg) diplotype and the intron 3 (+16bp)|exon 4 (Arg)|intron 6 (G) haplotype combinations are overrepresented in the breast cancer group, suggesting that the intron 3 (+16bp)|exon 4 (Arg) alleles may play a role in breast carcinogenesis. CONCLUSION: We conclude that two haplotypes harboring the intron 3 polymorphic (+16bp) allele are associated with a higher risk of breast cancer in the Turkish population.


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