***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Vascular endothelial growth factor ( VEGF ) plays an important role in cervical carcinogenesis . We hypothesized that VEGF genetic polymorphisms may affect cancer susceptibility , angiogenesis , and survival in patients with early cervical cancer . METHODS Among 215 healthy subjects and 199 early cervical cancer patients who were treated with surgical resection  , we specifically investigated four genetic polymorphisms within the VEGF gene ( -2578C > A , -460 T > C , + 405G > C , and + 936C > T ) .  VEGF and CD31 microvessel density ( MVD )  were measured using tissue microarrays constructed from 117 patients who had available tissue . RESULTS Risk of cervical cancer was decreased in subjects with the VEGF -2578A/A genotype ( adjusted OR=0.39 , 95 % CI 0.16 - 0.96 ) . Angiogenesis measured by CD31 MVD was significantly decreased in patients with the VEGF + 405C/C genotype and VEGF -2578C - -460 T - + 405C haplotype ( recessive model ; adjusted OR=0.32 , 95 % CI 0.11 - 0.99 , equally ) . Moreover , VEGF + 405C/C and VEGF -2578C - -460 T - + 405C haplotype were significantly related to shorter disease-free survival ( adjusted HR=3.18 , 95 % CI 1.13 - 8.94 , equally ) and overall survival ( adjusted HR=8.86 , 95 % CI 1.40 - 56.08 , equally ) by multiple Cox regression analysis . CONCLUSION Polymorphisms of VEGF genes may affect cancer susceptibility and survival of early cervical cancer by modulating tumor angiogenesis . Prospect i ve study among homogeneously treated patients is warranted Summary Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases , including aurora-A , B , and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib , to clarify the interpatient variability in exposure . In addition , this study explores the relationship between target receptor polymorphisms and toxicity of danusertib . Methods For associations with clearance , 48 cancer patients treated in a phase I study were analyzed for ABCB1 , ABCG2 and FMO3 polymorphisms . Association analyses between neutropenia and drug target receptors , including KDR , RET , FLT3 , FLT4 , AURKB and AURKA , were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials . Results No relationships between  danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found . Only , for the one patient with FMO3 18281AA polymorphism , a significantly higher clearance was noticed , compared to patients carrying at least 1 wild type allele . No effect of target receptor genotypes or haplotypes on neutropenia was observed . Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity , it is unlikely that danusertib is highly susceptible for pharmacogenetic variation . Therefore , no dosing alterations of danusertib are expected in the future , based on the polymorphisms studied . However , the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research , as we could study only a small group of patients Purpose : Vascular endothelial growth factor ( VEGF ) promotes angiogenesis and vascular permeability . The VEGF gene is polymorphic . We investigated the prognostic significance of three VEGF single nucleotide polymorphisms ( SNP )  in esophageal cancer . Experimental Design : Three hundred sixty-one patients were genotyped for three VEGF SNPs ( −460T/C , 405G/C , and 936C/T ) using DNA extracted from prospect ively collected blood sample s. The association of each individual SNP , and haplotypes of the three SNPs , on overall survival ( OS ) was investigated . Results : The variant allele of 936C/T was associated with improved OS compared with the wild-type genotype ( log-rank P < 0.001 ) . This association remained significant for OS after adjustments for age , gender , performance status , and disease stage [ VEGF 936C/T : adjusted hazard ratio ( AHR ) , 0.70 ; 95 % confidence interval ( 95 % CI ) , 0.49 - 0.99 ; P = 0.04 ; VEGF 936T/T : AHR , 0.11 ; 95 % CI , 0.02 - 0.82 ; P = 0.03 ] . No independent associations were found for VEGF −460T/C and VEGF 405G/C. The CGC haplotype of the three VEGF SNPs ( −460T/C , 405G/C , and 936C/T ) combined was associated with reduced OS compared with all other patients ( CGC/CGC : AHR , 1.51 ; 95 % CI , 1.00 - 2.30 ; P = 0.05 ) . Conclusions : VEGF 936C/T , and a haplotype of 460T/C , 405G/C , and 936C/T combined , has potential prognostic significance in esophageal cancer Purpose : This study was design ed to evaluate the associations between angiogenesis gene polymorphisms and clinical outcome in ovarian cancer patients treated with low-dose cyclophosphamide and bevacizumab .  Experimental Design : Seventy recurrent/metastatic epithelial ovarian cancer patients were enrolled in a phase II clinical trial . Genomic DNA was available from 53 blood sample s. Polymorphisms were analyzed using the PCR-RFLP protocol . A 5′ end 33P γATP-labeled PCR protocol was used to analyze dinucleotide repeats . Results : Patients genotyped A/A or A/T for the IL-8 T-251A gene polymorphism had a statistically significant lower response rate ( 19 % ; 0 % ) than those homozygous T/T ( 50 % ; P = 0.006 , Fisher 's exact test ) . Patients carrying a minimum one C allele ( C/C ; C/T ) of the CXCR2 C+785 T polymorphism showed a median progression-free survival ( PFS ) of 7.4 months compared with the PFS of 3.7 months for those homozygous T/T ( P = 0.026 , log-rank test ) . Patients with the VEGF C+936 T polymorphism C/T genotype had a longer median PFS of 11.8 months , compared with those with the C/C and T/T genotype , which had median PFS of 5.5 months and 3.2 months , respectively ( P = 0.061 , log-rank test ) . Patients carrying both AM 3′end alleles < 14 CA repeats had the shortest median PFS of 3.4 months ; patients with at least one allele > 14 repeats or both alleles > 14 repeats showed a median PFS of 6.4 months and 7.2 months , respectively ( P = 0.008 , log-rank test ) . Conclusion : Our data suggest that the IL-8 A-251 T polymorphism may be a molecular predictor of response to bevacizumab-based chemotherapy . The CXCR2 C+785 T , VEGF C+936 T single nucleotide polymorphisms and the AM 3′ dinucleotide repeat polymorphisms may be molecular markers for PFS in ovarian cancer patients Current prognostic factors for acute myeloblastic leukemia ( AML ) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment . Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses . We used the allelic discrimination method to identify polymorphisms in GSTT1 , SULT1C2 , CDA , SXR ( drug metabolic pathways ) , XPD , XPA , XPG , ERCC1 , TOP2A ( DNA repair ) , VEGF ( angiogenesis ) , and MDR1 ( multidrug resistance ) genes in 110 adult patients with intermediate-risk AML , enrolled in the CETLAM-99 prospect i ve trial . A multivariate prognostic model adjusted for age , white blood cell ( WBC ) count , French-American-British group , cytogenetics , MLL rearrangement , internal t and em duplication of FLT3 ( FLT3-ITD ) , induction courses to achieve complete remission , and germline polymorphisms , was used to detect independent risk factors associated with clinical outcome . This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles ( RR = 14 ; P = .02 ) . In the same model , increased relapse risk was associated with SULT1C2 heterozygosity ( RR = 4.1 ; P = .004 ) , FLT3-ITD ( RR 3.3 ; P = .003 ) , and MDR1 variant alleles ( RR = 2.4 ; P = .02 ) . Adverse prognostic variables for overall survival were XPA ( RR = 3.4 ; P = .02 ) and MDR1 ( RR = 2.1 ; P = .02 ) variant alleles , and WBC count ( RR = 2.1 ; P = .02 ) . These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML PURPOSE No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer . Vascular endothelial growth factor ( VEGF ) genetic variability has been associated with altered risk of breast cancer and variable promoter activity . Therefore , we evaluated the association of VEGF genotype with efficacy and toxicity in E2100 , a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer . PATIENTS AND METHODS DNA was extracted from tumor blocks of patients from E2100 . Three hundred sixty-three sample s were available to evaluate associations between genotype and outcome . Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2 . Testing for associations between each polymorphism and efficacy and toxicity was performed . RESULTS The VEGF-2578 AA genotype was associated with a superior median overall survival ( OS ) in the combination arm when compared with the alternate genotypes combined ( hazard ratio = 0.58 ; 95 % CI , 0.36 to 0.93 ; P = .023 ) . The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm ( hazard ratio = 0.62 ; 95 % CI , 0.46 to 0.83 ; P = .001 ) . Two additional genotypes , VEGF-634 CC and VEGF-1498 TT , were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined ( P = .005 and P = .022 , respectively ) . CONCLUSION Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer Summary Purpose Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor ( KDR ; VEGFR-2 ) and fms-related tyrosine kinase 4 ( FLT4 ; VEGFR-3 ) . This study aims at the identification of relationships between single nucleotide polymorphisms ( SNPs ) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure . In addition , the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored . Methods Blood sample s from 33 patients enrolled in a phase I dose-escalation study of telatinib  were analyzed . For correlation with dose normalized AUC(0–12 ) , ATP-binding cassette ( ABC ) B1 ( ABCB1 ) , ABCC1 , and ABCG2 were the genes selected . For correlation with telatinib  toxicity , selected genes were the drug target genes KDR and FLT4 . Results No association between dose normalized AUC(0–12 ) and drug transporter protein polymorphisms was observed . In addition , no association between toxicity and KDR or FLT4 genotype or haplotype was seen . Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib Endostatin inhibits endothelial cell proliferation and migration , prerequisites of angiogenesis . A functional missense mutation ( D104N ) in endostatin was associated with an increased  prostate cancer  risk in a small study . We undertook a larger , prospect i ve study within the Physicians ' Health Study to examine D104N and prostate cancer risk and progression among 544 incident prostate cancer cases 
    Output:
    
There was marked inter- and intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy .
Variants ( heterozygotes and /or homozygotes ) of VEGF + 405G > C were significantly associated with improved survival in a meta- analysis of multiple cancer sites