Three vascular endothelial growth factor polymorphisms (-460C>T, -2578C>A, 1612G>A) with cancer risk: a meta-analysis based on 30 case-control studies

We evaluated cancer risk with three VEGF polymorphisms (-460C>T, -2578C>A, 1612G>A) based on current available studies. -460C>T did not appear to influence cancer risks. -2578C carriers had a 30% reduction of colorectal cancer (CRC) risk in comparison with AA homozygote (OR: 0.70, CI: 0.56-0.88). 1612G carriers had a striking 84% reduction of gastric cancer risk in comparison with AA homozygote. Multiple pair-wise comparisons suggested a recessive role for both -2578A and 1612A risk allele. Further studies with larger samples, well-matched controls and homogenous ethnic background are warranted to confirm these findings. We recommend more efforts into the investigation of 1612G>A with cancer risks.     

Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia

Aim: microRNA-423 is an oncogenic factor which is frequently upregulated in cancer. However, associations withbreast cancer risk remain inconsistent. Therefore, we investigated the prevalence of microRNA-423 rs6505162C>Tgene variation with breast cancer susceptibility in Saudi women. Methodology: This study was conducted on 100breast cancer patients and 124 matched healthy individuals. Genotyping of the microRNA-423 rs6505162C/T genevariation was performed by using the amplification refractory mutation system PCR method (ARMS-PCR). Results:A significant difference was observed in the genotype distribution between the breast cancer cases and controls(p=0.0001), the frequencies of the genotypes CC,CT and TT being 25%, 52% and 23% in patients and 65%,20% and15% respectively, in controls. The microRNA-423 C>T variant was associated with an increased risk of breast cancerin codominant models for (OR = 6.73, 95 % CI, 3.50-12.97; RR 2.35(1.67-3.30, p=0.0001) the microRNA-423TTgenotype and (OR = 4.14, 95 % CI, 1.93-8.87; p=0.0003) microRNA-423CT (OR= 6.73, 95% CI, 3.50-12.97; p=0.0001)and also with the dominant model (OR 5.6(3.14-1.01), p=0.0001) CT+TT vs CC) with a non-significant association forthe recessive model (OR=1.75, 95%CI=0.08-3.44, P=0.139, TT vs CC+CT). The T allele significantly increased therisk of breast cancer (OR =2.63, 95 % CI, 1.77-3.91; p=0.001) compared to the C allele. Some 6.73 ,4.14 and 2.63 foldincreased risk of developing breast cancer was associated with TT and CT genotypes and the T allele of microRNA-423in the northwestern region of Saudi Arabia. Conclusion: Our findings indicate that the microRNA-423 TT genotypeand the T allele are associated with an increased susceptibility, metastasis and advanced stage of breast cancer in SaudiArabian patients. Further studies with larger sample sizes are necessary to confirm our findings.     

VEGF基因多态性与肺痛遗传危险因素的关系

Objective:We investigated the potential association between vascular endothelial growth factor (VEGF) poly-morphisms and the risk of lung cancer. Methods:In the case-control study, we used PCR-RFLP technique to determine two VEGF genotypes-2578C/A and 936C/T in 171 lung cancer patients and 172 healthy controls for conformation, and construct-ed haplotypes of the two gene sites by PHASE1.0 software. Unconditional logistic regression model was used to analyze the statistical association of genontypes or haplotypes in the two groups adjusted by gender and age. Results:Compared with at least one -2578A allele, individuals with-2578CC genotype found associated with a significantly decreased risk of lung can-cer [P=0.001;adjusted odds ratio (OR), 0.391;95% confidence interval (95% CI), 0.226-0.686]. Analyses stratified by gender showed that the combined -2578 CA and AA genotype were also associated with a significantly decreased risk of lung cancer. (P=0.016;OR 0.303;95% CI=0.153-0.601 and P=0.018;OR=0.547;95% CI=0.331-0.903, respectively). The distribu-tion of the two haplotypes (936C/-2578C and 936C/-2578A) were significantly different between case-and -control groups (P = 0.016, OR=0.317, 95% CI=0.124-0.809 and P=0.018, OR=0.547, 95% CI=0.331-0.903). Analyses categorized by tumor histology showed that Haplotype C-C was associated with a significantly decreased risk of adenocarcinoma compared with the reference haplotypes. (P=0.004;OR=0.237;95% CI=0.090-0.627). Conclusion:These results suggest that the VEGF polymorphisms may be a critical factor for the risk of lung cancer.     

Vascular endothelial growth factor -634G/C and vascular endothelial growth factor -2578C/A polymorphisms and lung cancer risk: a case–control study and meta-analysis

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. In present study, we conducted a case–control study and meta-analysis to evaluate the genetic effects of VEGF -634G/C and VEGF -2578C/A polymorphisms and risk of lung cancer. A total of 175 subjects were recruited for case–control study and seven studies were included in the meta-analysis. Our case–control study showed that VEGF -634G/C polymorphism had no association with lung cancer risk (CC vs. GG: OR?=?0.88, 95 % CI?=?0.37–2.11), whereas there was an association between VEGF -2578CC genotype and decrease in lung cancer risk (CC vs. CA/AA: OR?=?0.52, 95 % CI?=?0.28–0.96). A meta-analysis was further performed and statistically similar results were obtained (CC vs. GG: OR?=?0.91, 95 % CI?=?0.60–1.39 for VEGF ?634; CC vs. AA: OR?=?0.53, 95 % CI?=?0.32–0.89 for VEGF ?2578). Our study showed that the variant genotypes of the VEGF -2578C/A polymorphism, but not the VEGF -634G/C polymorphism, was associated with lung cancer risk. More studies are needed to detect VEGF -634G/C and VEGF ?2578 polymorphisms and their association with lung cancer in different ethnic populations incorporated with environmental exposures.     

Polymorphisms of tumor necrosis factor-alpha and breast cancer risk: a meta-analysis

We conducted a meta-analysis to assess the association between tumor necrosis factor-alpha (TNF-alpha) gene TNFA -308 (G>A), TNFA -238 (G>A), TNFA -857 (C>T), TNFA -863 (C>A), TNFA -1031 (T>C), TNFA -1210 (A>T) polymorphisms and breast cancer(BC) susceptibility. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African). An extensive search was performed to identify all case-control studies investigating such association. Thirteen eligible studies, including 10,236 BC patients and 13,143 controls, were identified. No significant association was observed in all genotypes in worldwide populations, but stratification by ethnicity indicated that the TNFA -308 A allele was associated with a decreased risk of BC compared with the G allele in Caucasian individuals (OR = 0.927, 95%CI = 0.879-0.978). Similar results were obtained when the A/A +A/G genotype was compared with the G/G genotype. In addition, meta-analysis results indicated that the A/A genotype of TNFA -308 was a risk factor for BC in African (A/A vs. G/G OR = 4.085 95%CI = 1.460-11.425; A/A vs. G/A OR = 4.861 95%CI = 1.746-13.527; A/A vs. G/A + G/G OR = 4.246 95%CI = 1.551-11.625), but not in Caucasian or Asian individuals. In conclusion, the results of this meta-analysis indicate that the TNFA -308 A allele may be an important protective factor for BC in European individuals, but it is not likely to confer susceptibility to BC in worldwide populations. In addition, the AA genotype of TNFA -308 may be a risk factor for BC in African individuals. Besides, other polymorphisms were not associated with BC susceptibility.     

Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis

Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated tobe associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, weperformed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studiesassessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studieswith 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between thers1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29,95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (Cvs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR=1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studieswas also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphismwith BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggeststhat IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, butnot by ethnicity.     

A Germline Mutation in the BRCA1 3’UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression and altered responses to externalstimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in womenwas also assessed but the conclusions were inconsistent. The present study concerns the relationship between theBRCA1-3’UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of SaudiArabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls fromthe northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3’UTR germlinevariant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results:The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% andin healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to besignificantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32,1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). Therewere 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in ourcases. A significant correlation was also found between the BRCA1 3’UTR variants with the stage of the disease anddistant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the3’untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breastcancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studiesare needed to confirm this finding in other regions of Saudi Arabia.     

Association of +405C>G and +936C>T Polymorphisms of the Vascular Endothelial Growth Factor Gene with Sporadic Breast Cancer in North Indians

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has beenimplicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluatethe relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancerin Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patientsand 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>Gpolymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observedsignificantly increased frequency of GG genotype in cases as compared to controls and strong association of+405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003).For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observedwith elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GGCTof +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk ofbreast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associationsof VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab,North India.     

Associations between vascular endothelial growth factor polymorphisms and prostate cancer risk: a meta-analysis

Angiogenesis is crucial for the development and metastasis of common cancers, and vascular endothelial growth factor (VEGF) is a key mediator in the process of angiogenesis. Numerous studies assessed the associations of VEGF 1154G/A and 2578C/A polymorphisms with prostate cancer risk, but the results were inconsistent. We performed a meta-analysis to investigate the possible associations. Relevant studies were searched in PubMed and Embase databases. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to evaluate the associations. Finally, eight individual case–control studies from seven publications were finally included into the meta-analysis. There were a total of 3,879 cases and 4,285 controls from those eight studies. Meta-analysis of those four case–control studies for VEGF 1154G/A polymorphism showed that VEGF 1154G/A polymorphism was weakly associated with risk of prostate cancer under the allele model (A versus G: OR?=?0.68, 95 % CI 0.46–1.00, P?=?0.05). Meta-analysis of four case–control studies for VEGF 2578C/A polymorphism showed that there was an association between VEGF 2578C/A polymorphism and prostate cancer under the recessive model (AA versus CC/CA: OR?=?1.53, 95 % CI 1.01–2.30, P?=?0.04). However, there was no obvious association in the other comparison models. Therefore, there is limited evidence for the associations of VEGF 1154G/A and 2578C/A polymorphisms with prostate cancer risk, and more studies are needed to further assess the associations above.     

Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis.

PURPOSE: Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator of breast cancer angiogenesis. Therefore, we investigated the association of polymorphisms in the VEGF gene with breast cancer risk and prognostic characteristics of the tumors in a large case-control study. EXPERIMENTAL DESIGN: We examined three polymorphisms in the VEGF gene (-2578C/A, -1154G/A, and +936C/T) in 571 familial breast cancer cases from Poland and Germany and -2578C/A, -634G/C, and +936C/T polymorphisms in 974 unselected breast cancer cases from Sweden together with ethnically and geographically selected controls. RESULTS: None of the polymorphisms or any haplotype was significantly associated with either familial or unselected breast cancers. Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the unselected cases for genotypes or haplotypes that associated with tumor characteristics. The -634CC genotype and the -2578/-634 CC haplotype were significantly associated with high tumor aggressiveness (large tumor size and high histologic grade, P < 0.01) and the -2578AA genotype and the -2578/-634 AG haplotype with low histologic grade tumors (P = 0.04). The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. CONCLUSIONS: Although none of the polymorphisms studied in the VEGF gene was found to influence susceptibility to breast cancer significantly, some of the VEGF genotypes and haplotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis.     

Association between Polymorphisms of ERCC5 Gene and Susceptibility to Gastric Cancer: A Systematic Review and Meta-Analysis

Background: several epidemiological studies have suggested that polymorphisms of the Excision Repair Cross Complementing Group-5 (ERCC5) gene might be related to gastric cancer risk; however, the results have been inconsistent or controversial. Therefore, we have performed a systematic review and meta-analysis to clarify the association between the ERCC5 gene polymorphisms and gastric cancer risk. Materials and Methods: An electronic search was conducted of several databases, including PubMed, Web of Science, and Google Scholar for articles that describe the association between polymorphisms of the ERCC5 gene and susceptibility of gastric cancer. Results: A total of 33 case control studies in 15 publications were included in the present meta-analysis. There were significant associations between gastric cancer susceptibility and ERCC5 gene rs751402 C>T (T vs. C: OR = 1.166, 95% C = 1.066-1.274, p= 0.001; TT vs. CC: OR = 0.723, 95% CI = 0.587-0.890, p = 0.002; TT+TC vs. CC: OR = 0.853, 95% CI = 0.757-0.961, p = 0.009; TT vs. TC+CC: OR = 0.793, 95% CI = 0.659-0.955, p = 0.015), rs2296147 T>C (C vs. T: OR = 1.268, 95% C = 1.049-1.532, p= 0.014), rs873601 G>A polymorphisms (A vs. G, OR = 1.087, 95% C = 1.021-1.159, p= 0.010; AA vs. GG, OR = 1.184, 95% CI = 1.043-1.343, p = 0.009, AA vs. AG+GG, OR = 1.156, 95% CI = 1.040-1.284, p = 0.007), but not rs2094258 C>T and rs1047768 T>C. Conclusion: the current meta-analysis demonstrates that rs751402 C>T, rs2296147 T>C, and rs873601 G>A polymorphisms of ERCC5 gene are associated with the susceptibility of gastric cancer.     

Lack of Association Between the Matrix Metalloproteinase-2-1306C>T Polymorphism and Breast Cancer Susceptibility: a Meta-analysis

Background: Since inconsistent results have been reported regarding the relation between the matrix metalloproteinase-2 (MMP-2) -1306C>T polymorphism and susceptibility for breast cancer, we performed a meta-analysis to investigate the issue. Materials and Methods: An internet search of PubMed and EMBASE wasperformed to identify eligible studies. Pooled odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated to evaluate any association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility. Results: Nine case-control studies were included in the meta-analysis, involving 9,858 cases and 10,871 controls. Overall, there was no evidence of any association between the MMP-2 -1306C>T polymorphism and breast cancer susceptibility in different genetic models (T-allele vs C-allele: OR=0.95, 95%CI, 0.82-1.10, p=0.49; TT vs CC: OR=1.03, 95%CI, 0.90-1.19, p=0.66; TT+TC vs CC: OR=0.93, 95%CI, 0.78-1.10, p=0.38; TT vs TC+CC: OR=1.02, 95%CI, 0.89-1.17, p=0.77). In the subgroup analysis by ethnicity, CC was associated witha significant increase in breast susceptibility among Latin-Americans in the dominant model (OR=0.61, 95%CI,0.40-0.93, p=0.02), but the association disappeared in other models. No significant association was observed among Europeans, East Asians and others in different genetic models. In the subgroup analysis by their source of controls, no significant association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility was noted among population-based studies and hospital-based studies in different genetic models. Conclusions: The results of this meta-analysis suggest that MMP-2 -1306C>T polymorphism is not associated with breast cancer susceptibility, although the association among Latin-Americans in the dominant model was significant.     

Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies

Background: Previous epidemiological studies have suggested a potential role of the HSPA1B±1267A/G polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ±1267A/G was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p< 0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ±1267A/G polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.     

Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development,prognosis, and survival

Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the association of functional polymorphisms in the VEGF gene with colorectal cancer development, prognosis, and survival. Three hundred twelve consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin‐embedded tissue and five VEGF (?2578C>A, ?1154G>A, ?634G>C, ?460T>C, and +936C>T) gene polymorphisms were determined using a polymerase chain reaction‐restriction fragment length polymorphism assay. VEGF ?2578C>A, ?1154G>A, ?634G>C, ?460T>C, and +936C>T genotype and allele frequencies were similar among patients and controls. There was a trend showing carriers of the ?2578A and +936T alleles more frequent among patients with CRC, but these differences did not reach statistical significance. Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. However, the ?2578AA, ?634CC, and +936TT genotypes found to be related with a significantly lower overall survival in our study. In conclusion, VEGF gene polymorphisms were found to be an independent prognostic marker for Greek CRC patients. © 2008 Wiley‐Liss, Inc.     

Perceived Barriers to Breast Cancer Screening among Saudi Women at Primary Care Setting

Introduction: Screening for breast cancer (BC) is of low rate in Saudi Arabia; although it is provided in the country free of charge to the population. This cross-sectional study aimed at investigating the perceived barriers towards BC screening in Al Hassa, Saudi Arabia. Participants and Methods: A total of 816 adult Saudi women aged ≥ 30 years attending for routine primary health services or accompanying patients at the selected primary health care centers (PHCs) were randomly selected from 12 PHCs (8 urban and four rural) using multi-stage sampling method. Participants were invited to personal interview using semi-structured data collection instrument including inquiries about socio-demographics, reproductive history, previous histories of diagnosed breast lesions and breast cancer. The perceived individual barriers towards screening, their attitudes, the reasons for not attending previously held screening campaigns in Al Hassa, were also included. Results: Low utilization of BC screening has being significantly associated with woman’s age (OR=2.55; 95% CI= 1.71-3.83), higher educational status (OR=2.98; 95% CI=2.05-4.34), higher family income (OR=1.96; 95% CI=1.31-2.93), using hormonal contraception (OR=1.46; 95% CI=0.99-2.13) and positive history of previous breast (OR=12.16; 95% CI=6.89-21.46), as shown by the results of the logistic regression model. Exploratory factor analysis showed that personal fears (especially fear of doctors/examiners, fear of hospitals and health facilities and fear of consequences/results) were the major factors that hinder women from utilizing the free of charge BC screening with high loading eigenvalue of 3.335, explaining 30.4% of the barriers. Conclusion: Educational interventions aim at improving breast cancer knowledge and addressing barriers should be incorporated as core component of the screening program in Saudi Arabia.     

Polymorphism of vascular endothelial growth factor �C2578C/A with cancer risk: evidence from 11263 subjects

Published data on the association between vascular endothelial growth factor (VEGF) ?C2578C/A polymorphism and cancer risk is inconclusive. To derive a more precise estimation of association between VEGF ?C2578C/A polymorphism and the risk of cancer, we performed a meta-analysis of 5415 cancer cases and 5848 controls from 16 published case?Ccontrol studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Our meta-analysis indicated that VEGF ?C2578C/A polymorphism was associated with the risk of colorectal cancer under homozygote comparison (OR?=?0.70, 95% CI?=?0.53?C0.92), dominant model (OR?=?0.72, 95% CI?=?0.57?C0.92), and recessive model (OR?=?0.82, 95% CI?=?0.67?C1.01), although no evidence of association between VEGF ?C2578C/A polymorphism and cancer risk was observed as we compared in the pooled analyses (homozygote comparison: OR?=?0.97, 95% CI?=?0.81?C1.16). More studies are needed to detect VEGF ?C2578C/A polymorphism and its association with cancer in different ethnic populations incorporated with environmental exposures in the susceptibility of different kinds of cancer.     

Association of polymorphisms of angiogenesis genes with breast cancer

BACKGROUND: Few studies have systematically explored a pathway approach: to test the association of multiple polymorphisms from multiple genes important to angiogenesis simultaneously with risk of breast cancer. We report our preliminary data evaluating the association of polymorphisms from seven genes known to influence angiogenesis with the likelihood of having breast cancer. METHODS: We recruited 715 controls and 520 subjects with breast cancer. Subjects provided a blood specimen and completed a questionnaire that included common breast cancer risk factors and breast cancer status. We evaluated candidate polymorphisms in the following genes: Hypoxia Inducible Factor-1 alpha (HIF1alpha), Vascular Endothelial Growth Factor (VEGF), VEGF Receptor 1 (VEGFR-1), VEGFR-2, endothelial Nitric Oxide Synthase (eNOS), Neuropilin-1 (NRP-1) and Neuropilin-2 (NRP-2). Testing for associations between each polymorphism and the presence or absence of breast cancer was performed. RESULTS: VEGF-2578 AA and -1498 CC genotypes were more common in cancer cases than controls (P = 0.06 and P = 0.04, respectively). These two genotypes remained significant predictors of breast cancer status after adjusting for non-genetic risk factors estimated by the Gail model (P = 0.03 and P = 0.03, respectively). When comparing women with invasive versus pre-invasive breast cancer, the eNOS-786 TT and eNOS 894 GG genotypes were associated with a greater likelihood of invasive disease and the eNOS 894 GG genotype was associated with a greater likelihood of having metastatic disease. CONCLUSION: There is an association of the VEGF-2578A and -1498C alleles with increased breast cancer risk. This association remains significant when adjusted for Gail score-related risk factors.     

Genetic Effects of Vascular Endothelial Growth Factor A (VEGF-A) and Its Association with Disease Progression in Breast Cancer Population of Saudi Arabia

Aim: Previous studies have shown that vascular endothelial growth factor (VEGFA) gene variants were associated with breast cancer risk. The goal of the current study was to evaluate the genetic effects of the vascular endothelial growth factor (VEGF) on the risk of breast cancer and its association with disease progression. Methodology: This case control study was conducted on 110 Breast cancer cases and 110 gender matched healthy controls. Vascular endothelial growth factor A (VEGF-A) 1 (-460T>C) genotyping was performed using Amplification refractory mutation system PCR method. The vascular endothelial growth factor A (VEGF-A) (-460T>C) genotypes were collated with different clinicopathological features of breast cancer patients. Results: A significant difference was observed between the genotype distribution of VEGF-A (-460T>C) among breast cancer cases and gender matched healthy controls (p=0.006). The frequencies of all three genotypes CC,CT,TT reported in the breast cancer patients and sex matched healthy controls were  4.54%, 46.36% ,49.20%  and 7.27%, 64.54%, 28.18% respectively. The increased susceptibility to breast cancer disease was found to be associated with VEGF (-460T>C) CC vs TT variant in codominant inheritance model OR 2.78 (0.83-9.26) RR 1.68(1.01 to 2.81) P=0.04. A significant association was reported with VEGF (-460T>C) (CC+CT vs. TT) variant in recessive inheritance model, (OR=2.45 (95% CI= (1.40-4.29), P=0.003. Our findings indicated that VEGF (-460T>C) TT genotype is associated with an increased susceptibility to breast cancer disease. Our result indicates a potential dominant effect of VEGF (-460T>C) TT genotype on susceptibility to the breast cancer disease. Conclusion: VEGF (-460T>C) TT genotype significantly increased the risk of breast cancer. VEGF-A (-460T>C) genetic ariability was significantly associated with distant metastasis of the disease. It may be a useful as predisposing genetic marker for breast cancer .Further studies with larger sample sizes are necessary to confirm our findings.     

CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations

ABSTRACT: INTRODUCTION: It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage, case control study, we determined whether common functional tagSNPs (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis. METHODS: Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied. RESULTS: Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 3.15, P = 0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P < 0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P < 0.001) and western blotting (P = 0.001) results. CONCLUSION: These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.