Yazan: admin Tarih: Ağu 4th, 2008 | Kategori::
Gene polymorphisms
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Department of Toxicology, Gazi University, Faculty of Pharmacy, Ankara, Turkey.
Humans are routinely exposed to mutagenic and carcinogenic chemicals. These chemicals can form DNA adducts in vivo and thus lead to DNA damage. The integrity of most of the so-damaged DNAs is typically restored as a consequence of the action of certain DNA-repairing enzymes. In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. XRCC1 is a base-excision repair protein that plays a central role in the repair of DNA base damage and strand breaks. Amongst the known genetic polymorphisms of the DNA-repair genes, X-ray repair cross-complementing groups 1 and 3 (XRCC1 and XRCC3) have been studied most commonly. Inconsistent results have been reported regarding the associations between the Arg399Gln (exon 10) polymorphism of XRCC1 and either functional significance or the risk of tobacco-associated cancers. The Gln allele of this polymorphism was associated with higher levels of DNA adducts. Therefore we genotyped one of the polymorphism of XRCC1, Gln allele. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. There has been no information on interindividual variability of Arg399Gln genotype in the Turkish population. Due to the association between the Arg399Gln polymorphism of XRCC1 and the risk of tobacco-associated cancers, we preferred to evaluate the allelic frequencies of Arg399Gln genotype than the other polymorphisms in XRCC1 gene in healthy Turkish population by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis to enable to show interindividual differences and compare to other populations.
Yazan: admin Tarih: Ağu 4th, 2008 | Kategori::
Pancreatic cancer(Pankreas kanseri)
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J Mol Med. 2006 Dec;84(12):1015-22. Epub 2006 Oct 13.
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Treiber M,
Schulz HU,
Landt O,
Drenth JP,
Castellani C,
Real FX,
Akar N,
Ammann RW,
Bargetzi M,
Bhatia E,
Demaine AG,
Battagia C,
Kingsnorth A,
O’Reilly D,
Truninger K,
Koudova M,
Spicak J,
Cerny M,
Menzel HJ,
Moral P,
Pignatti PF,
Romanelli MG,
Rickards O,
De Stefano GF,
Zarnescu NO,
Choudhuri G,
Sikora SS,
Jansen JB,
Weiss FU,
Pietschmann M,
Teich N,
Gress TM,
Ockenga J,
Schmidt H,
Kage A,
Halangk J,
Rosendahl J,
Groneberg DA,
Nickel R,
Witt H.
Department of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.
Yazan: admin Tarih: Ağu 3rd, 2008 | Kategori::
Lung cancer (Akciğer Kanseri)
J Carcinog. 2007 Sep 26;6:13.
Yedikule Teaching Hospital for Chest Diseases and Thoracic Surgery, Depertmant of Thoracic Surgery, Istanbul, Turkey. dradalet@hotmail.com.
ABSTRACT: BACKGROUND: Glutathione S-transferase (GSTs) plays an important role in the detoxification of many xenobiotics involved in the etiology of cancer. In different ethnic groups, variations in null allele frequency have been observed. We have investigated GSTM1 gene polymorphisms in healthy subjects and lung cancer patients in the Turkish population and reviewed the control subjects of the studies performed in the Turkish population. METHODS: Following blood sampling from patients and controls, DNA samples were extracted from the whole blood and were amplified by using polymerase chain reaction (PCR) method in all of the 256 cases, consisting of 102 previously diagnosed with lung cancer and 154 healthy controls. RESULTS: The prevalence of GSTM1-null genotype in the lung cancer patients was 49%, compared to 52.6% in the control group (OR = 1.39, 95% CI = 0.70-1.90, p = 0.57). There were also no significant relationships in GSTM1 genotypes among histopathologic types of lung cancers (p > 0.05). The frequency of GSTM1 was found to be 41.2% (n = 1809) when the control subjects of the studies performed in Turkish population were reviewed. CONCLUSION: We have observed that GSTM1 genotype is not an independent risk factor for lung cancer.
