Yazan: admin Tarih: Tem 23rd, 2010 | Kategori::
Lung cancer (Akciğer Kanseri)
Med Oncol. 2010 Jul 20.
Coskunpinar E, Eraltan IY, Turna A, Agachan B.
Department of Molecular Medicine, Institute of Experimental Medicine Research, Istanbul University, Vakif Gureba cad, Capa, 34093, Istanbul, Turkey.
Abstract
In this study, we aimed to investigate a possible association of the COX-2 polymorphisms with the risk of developing lung carcinoma. COX-2 (-765G–>C; -1195A–>G) gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 118 healthy individuals and 231 patients with lung carcinoma. The present study was the first that addressed the role of the COX-2-765G–>C and -1195A–>G polymorphisms in lung carcinoma in Turkish population. In the present study, we found that the frequencies of GG, CC, and CG genotypes of COX-2-765G–>C and AA, GG, and AG genotypes of -1195A–>G in our control group were 0.22, 0.22, 0.55 and 0.59, 0.0, 0.40, respectively. These frequencies in patient group were 0.34, 0.07, 0.58 and 0.74, 0.04, 0.24, respectively. There were statistically significant differences in COX-2-765G–>C (P = 0.0002) and -1195A–>G genotypes (P = 0.007) between the controls and patients. We found that individuals carrying -765 GG genotype and -765 G allele of COX-2 or 1195 AA genotype of COX-2 and -765G: -1195A haplotype had an increased risk for the development of lung carcinoma. In contrast, individuals with -765 CC, -1195 AG genotypes and -1195 G allele of COX-2 seem to be protective from lung carcinoma. We suggest that the COX-2-765G–>C and -1195A–>G genotypes may be a risk factor for lung carcinoma.
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.
Yazan: admin Tarih: Şub 11th, 2009 | Kategori::
Cancer (Kanser),
Lung cancer (Akciğer Kanseri),
MnSOD
Cancer Genet Cytogenet. 2009 Feb;189(1):1-4
Association between manganese superoxide dismutase polymorphism and risk of lung cancer.
Department of Biochemistry, Faculty of Pharmacy, Istanbul University, 34116, Beyazit Istanbul, Turkey.
Manganese superoxide dismutase (MnSOD) is one of the major enzymes responsible for the defense against oxidative damage due to reactive oxygen species (ROS) in the mitochondria. C–>T substitution in the MnSOD gene (SOD2) produces an Ala–>Val change at amino acid 16, in the mitochondrial targeting sequence of the MnSOD precursor. This seems to reduce transport of the enzyme into mitochondria, decreasing its defense capacity against oxidative stress. The present case-control study was conducted to investigate the association of SOD2 genetic polymorphism with individual susceptibility to lung cancer. Ala16Val polymorphisms were determined using polymerase chain reaction, restriction fragment length polymorphism mapping, and agarose gel electrophoresis techniques in 100 lung cancer patients and 50 healthy control subjects. The frequency of the Val allele (OR=1.297, 95% CI=1.095-1.536) and the Val/Val genotype (OR=7.00, 95% CI=2.282-21.476) was significantly higher in lung cancer patients than in control subjects. There was a combined effect of Val/Val genotype as a genetic factor with smoking as an environment factor (OR=2.24). The increase in risk of lung cancer was lesser with this combined effect than with the Val/Val genotype alone. Thus, the Val/Val genotype of SOD2 may be associated with lung cancer in a Turkish population.
Yazan: admin Tarih: Şub 3rd, 2009 | Kategori::
Lung cancer (Akciğer Kanseri)
Arh Hig Rada Toksikol. 2008 Dec;59(4):241-50.
The association of OGG1 Ser326Cys polymorphism and urinary 8-OHdG levels with lung cancer susceptibility: a hospital-based case-control study in Turkey.
Faculty of Pharmacy, Department of Toxicology, Gazi University, Ankara, Turkey. bensuka@gmail.com
High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.
