ABSTRACT
UNLABELLED: The angiogenesis is an important process in the pathogenesis of malignancies. It is regulated by various growth factors, with the vascular endothelial growth factor (VEGF) playing the central role. The aim of the present study was to evaluate possible associations of functional VEGF -2578C>A, -634G>C, and +936C>T polymorphisms with the risk for occurrence and progression of non-small cell lung cancer (NSCLC) in patients living in Republic of Belarus. MATERIALS AND METHODS: A total of 202 patients (147 males and 55 females) diagnosed as having the NSCLC. The control group consisted of 336 individuals (245 males and 91 females) without an oncopathology. The total DNA was isolated from peripheral blood. We investigated the single nucleotide polymorphisms of VEGF (rs 2010963), (rs 699947), (rs 3025039). The genotyping was performed by PCR-RFLP analysis. RESULTS: Our results revealed a marginally significant association of the -2578CC genotype (p=0.002) with a greater degree of tumor spread (Т2-Т4). Heterozygous genotypes -2578СРand +936СT carriers were included into the follow-up group significantly more often (Ñ=0.021 and Ñ=0.012, respectively). Our study demonstrate that VEGF -2578A/C and +936C/T polymorphisms are among the factors determining the individual peculiarities of NSCLC course in this population and can be used for clarifying the prognosis of the disease.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Transformation, Neoplastic/genetics , Lung Neoplasms/genetics , Vascular Endothelial Growth Factor A/genetics , Alleles , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Case-Control Studies , Cell Transformation, Neoplastic/metabolism , Disease Progression , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Polymorphism, Single Nucleotide , Risk Factors , Tumor Burden , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Imbalance between the phases of the biotransfotmation system (activation, detoxication and removal of toxic compounds) is one of the causes of multifactorial pathology developing. That is why study on the influence of the total contribution of polymorphic gene variants of xenobiotic biotransformation enzymes of all three phases on predisposition to lung cancer emergence is important. The aim of the work was to determine polymorphic variants of genes of xenobiotic biotransformation enzymes of lung cancer patients and to identify markers of predisposition to lung cancer. Association of homozygous GSTT1 gene deletion with predisposition to lung cancer was detected in residents of Belarus. Combinations of polymorphic gene loci of biotransformation enzymes exert a modifying effect on risk importance of GSTT1 genotype in lung cancer development. The combination 734AA CYP1A2/GSTT1(-)/GSTM1(+)/"slow" acetylator/3435CC MDR1 is of the highest risk importance. The combination "slow" acetylator/GSTT1(+)/ GSTM1(+) exerts a protective effect.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cytochrome P-450 CYP1A2/genetics , Genetic Predisposition to Disease , Glutathione Transferase/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/metabolism , Case-Control Studies , Cytochrome P-450 CYP1A2/metabolism , Female , Gene Deletion , Genetic Loci , Glutathione Transferase/metabolism , Homozygote , Humans , Inactivation, Metabolic/genetics , Lung Neoplasms/epidemiology , Lung Neoplasms/metabolism , Male , Middle Aged , Republic of Belarus/epidemiology , Risk Factors , Xenobiotics/metabolismABSTRACT
Carriers of GSTTI gene deletion were found to be more subjected to a risk of emerging non-small-cell lung cancer (NSLC) than those of normal GSTT1(+) genotype. Study on the relation between GST gene polymorphism and cytogenetic indices in lung cancer patients has shown a significant excess of the group average level in cells with micronuclei in NSLC patients with GSTTI(-). The frequency of cells with micronuclei was higher in smoking patients with a mutant genotype than in smoking carriers of the GSTT1(+) genotype.
