Genetic polymorphisms of vascular endothelial growth factor [VEGF] in Egyptian women with breast cancer

Background: Vascular endothelial growth factor [VEGF] was considered to have an association with breast cancer because it regulates endothelial cell proliferation,migration and differentiation

Subjects and methods: One hundred and fifty two women with breast cancer were compared to 100 healthy control Egyptian women recruited from the same locality. VEGF gene polymorphisms were assessed using the PCR-RFLP analysis of DNA samples obtained from peripheral blood.SNP scanning was performed using MnII, BsmfI, CviAII, BsmfI, MnII restriction enzymes for VEGF1154 G/A, 634 G/C, 405 C/G, 936 C/T, 1612 G/A polymorphisms, respectively

Results: Breast cancer among Egyptian women was strongly associated with the mutations related to VEGF gene polymorphism as follows: VEGF 1154 G allele frequency was significantly higher than the A allele [P = 0.0007,O.R =2.4], VEGF 634 C allele frequency was significantly higher than the G allele [P = 0.012, O.R =0.62],VEGF 405 C Allele frequency was significantly higher than G Allele [P = 0.009, O.R =1.67], VEGF 936 C Allele frequency was significantly higher than the T Allele [P = 0.0057, O.R =1.72], VEGF 1612 G Allele frequency was significantly higher than A allele [P = 0.0148, O.R =1.62]. For VEGF 1154 GA: AA vs. GA+GG [Recessive] P = 0.10, O.R = 6.23, C.I [1.0-38.9], GA vs. AA+GG [over dominant] P= 0.01[*], O.R = 2.13, C.I [1.2-3.8], AA+GA vs. GG [dominant] P= 0.0015[*], O.R = 2.57, C.I [1.5-4.5]. For VEGF 634 GC: CC vs. GC+GG [Recessive] P= 0.1852, O.R = 0.64, C.I [0.4-1.2], GC vs. CC+GG [over dominant] P= 0.2669, O.R = 0.71, C.I [0.4-1.2], CC+GC vs. GG [dominant] P = 0.0002[**], O.R=0.05, C.I [0.0-0.2].For VEGF 405 CG: GG vs. CG+CC [Recessive] P= 0.0013[*], O.R = NA,C.I =NA, CG vs. GG+CC [over dominant] P= 0.877, O.R = 1.08, [0.6-1.9], GG+CG vs. CC [dominant] P = 0.0323[*], O.R=1.93,C.I [1.1-3.4].For VEGF 936 CT: TT vs. CT+CC [Recessive] P = 0.1833, O.R = 1.63, C.I [0.9-3.1], CT vs. TT+CC [over dominant] P = 0.1379, O.R = 1.55, C.I [0.9-2.6], TT+CT vs. CC[dominant] P = 0.0075[**], O.R=2.08, C.I [1.2-3.5]. For VEGF 1612 GA: AA vs. GA+GG [Recessive] P = 0.0000[**], O.R = NA, C.I = NA, GA vs. AA+GG [over dominant] P= 0.0002[**], O.R = 0.36, C.I [0.6-0.2], AA+GA vs. GG [dominant] P = 0.9541, O.R = 0.95, C.I [1.6-0.6]

Gene polymorphisms of the DNA repairing genes APE1 and XRCC1 among smoking lung cancer Egyptians

Lung cancer is the leading cause of cancer-related mortality worldwide and is thus a major public health problem. DNA base damage or losses caused by endogenous and exogenous agents occur constantly at a high frequency in human cells. The removal or repair of damaged bases is an important mechanism in protecting the integrity of the genome. APE1 [Apurinic/Apyrimidinic Endonuclease 1] and XRCC1 [X-ray cross-complementing group1] are DNA repair proteins that play important roles in the base excision repair [BER] pathway. The focus of this work is limited to the association between polymorphisms in the DNA repair genes, [APE1 Asp148Glu [2197 T-G] and XRCC1 Arg399Gln [28152 G-A] genotypes], cigarette smoking and lung cancer. This study has included 131 cases affected with lung cancers include; 33 cases with small cell carcinoma [25.2%] and 98 cases with non-small cell carcinoma [74.8%]. They were recruited from oncology Center, Mansoura University, Egypt; in the period between April 2008 to March 2010. For comparison, a negative control group including 150 healthy individuals randomly selected from blood donors. Controls were selected by random sampling cancer-free individuals without a past history of cancer, who visited Mansoura University hospitals and provided peripheral blood between April 2008 and March 2010. DNA was extracted from the whole peripheral blood using generation DNA purification capture column kit [Gentra system, USA] and genotyping for APE1 Glu148Asp and XRCC1 Arg 399 Gln polymorphisms was performed by a PCR--CTPP [PCR with confronting two-pair primers] method. The collected data were organized and statistically analyzed using SPSS statistical computer package version 10 software. we observed that, There were no significant differences in the frequencies of the APE1 Asp148 Glu [2197 T-G] polymorphism of all genotypes and alleles in all lung cancer cases compared to all healthy controls. Also, there were no significant differences in the frequencies of all genotypes and alleles in lung cancer cases compared to controls of all smoking status. While, in former smoking individuals; significant difference in the frequency of the mutant GG genotype in lung cancer cases compared to controls [p-value=0.003]. We observed that, There were no significant differences in the frequencies of the XRCC1 Arg 399 Gln [28152 G-A] polymorphism of all genotypes and alleles in all lung cancer cases compared to all healthy controls. Also, there were no significant differences in the frequencies of all genotypes and alleles in lung cancer cases compared to controls of all smoking status. While, in never smoking individuals; significant difference in the frequency of the mutant AA genotype in lung cancer cases compared to controls [p-value=0.0004]

Characterization of angiotensin converting enzyme gene polymorphism and risk of different heart diseases

The present work aims to test the association of angiotensin converting enzyme [ACE] gene insertion/ deletion [I/D] polymorphism in patients with myocardial infarction [MI]. The study comprised 79 Egyptian cases with MI. Their mean age was 54.4 +/- 9.9 years including 60 [75%] males and 19 [24.1%] females, 23 [29.1%] were smokers, 21 [26.6%] had a positive family history of MI, 25 cases [31.6%] were diabetic, 16 cases [20.3%] were hyperlipidemic. For comparison, 238 healthy subjects of nearly matched age and sex, with no history of any cardiac diseases were taken as a control group. For all subjects, DNA testing for ACE gene I/D polymorphism was done using PCR amplification to detect both D and I alleles followed by a second run PCR specific for the I allele for cases typed as DD in the first run. Cases had higher frequency of DD [29.1%] and ID [62%] than II [8.9%] genotype with a higher frequency of D allele than I allele [64.4% vs 33.6%]. Compared to controls, cases had significantly higher frequency of ID genotype [62% versus 47.5%, P < 0.05]. Cases with low risk factors had a higher frequency of ID genotype compared to controls [66.7% vs 47.5%, P = 0.002]. The same was, also, found in the high risk group but with a lower level of significance [63.6% vs 47.5%, P = 0.041]. ACE gene polymorphism is probably a risk factor for ischemic heart disease among Egyptian cases particularly if integrated with other environmental and genetic risk factors

DNA ploidy and expression of P53, cMyc in childhood leukemia's and their families

Chromosomal abnormalities in childhood leukemia have important biological, diagnostic and prognostic significance. The genes that are associated with the development of malignancy were categorized as oncogenes and tumor suppressor genes. P53 belongs to the category of tumor genes and is located on the short arm of chromosome 17 p13. It is a specific transcriptional activator of genes controlling GI checkpoint of the cell cycle and controls the expression of certain genes involved in the control of programmed cell death [Apoptosis]. cMyc gene is Juxtaposed with one of the immunoglobulin genes: heavy chain on 14[q32], kappa on 2[p12] or Iambda on 22[q11]. In pediatric ALL with translocation of ch.,8 [q24] onch., 14[q32] or ch22[q11], c-Myc expression is markedly deregulated by the highly active immunoglobulin locus. This leads to an increase in c-Myc max dimmers and transactivation of multiple cognate target genes, driving uncontrolled cellular proliferation. This study was designed to determine the DNA content [ploidy], expression P53 protein and c-Myc protein in children with acute lymphoblastic leukemia as well as in their first degree relatives [parents and siblings] in order to detect the role of these proteins in the developing of leukemia and those at risk of developing leukemia This study was done on 20 infants and children [16 males and 4 females], their age ranged from 2 to 12 years. They were admitted to the Hematology Unit at Mansoura University Children Hospital where they were diagnosed as acute lymphoblastic leukemia [ALL] and were taken at presentation before induction of treatment. Their first-degree relatives were also included in the study [20 fathers, 20 mothers and 44 siblings [23 brothers and 21 sisters]].Twenty healthy persons with negative family /history of cancers, their aye range from 4 to 30 years, were taken as control group. All the studied subjects were subjected to isolation of lymphocyte which staining and fixation within 24 hours from sampling where DNA analysis by flow cytometer was done. The results proved that 60 % of the cases with acute lymphoblastic leukemia were hyper diploid [DWA index >1.0] and 10 % were hypo diploid [DNA index [1.0]. All of their leukemic children were DNA aneuploid while 10 % of tile-studied parents had DNA aneuploid positive cells and 7% of the healthy siblings had DNA aneuploid positive cells. A high significant level of p53 protein in patients with ALL when compared with healthy controls [p<0.0001], a significant difference in between patients with ALL and their first -degree relative regarding P53 protein. Also a significant difference in between the first-degree relative and healthy controls regarding p53 [p=<0.0001]. The results of this study also showed significant difference in the level of expression of p53 protein among patients with DNA aneuploidy cells compared to those with DNA diploid patients. A significant difference in patients with ALL when compared with healthy controls, also were was significant difference in first degree relatives of leukemia patients versus to healthy controls regarding the level of c-Myc protein [p=<0.0001]. 80 % of parents and 77 % of siblings between the first-degree relative expressing high levels of cMyc protein

Conclusion: genetic alterations play an important role in the development of childhood leukemia particularly mutation of p53 tumor suppressor gene and cMyc gene where the level of expression of their related protein is high. Also change in the DNA content of the lymphoblast's of majority of the patients with acute lymphoblastic leukemia appears to be constant feature. These changes not only present in cases with ALL but also in their first degree relatives suggesting that there is a vertical transmission of these genes in these families. First -degree relatives of leukemia patients particularly those with abnormal DNA and those expressing high level of p53 protein and cMyc protein are at high risk of developing cancers must be subjected for close follow up