***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 OBJECTIVES The appropriate sequencing of chemotherapy and radiation for the treatment of advanced endometrial cancer has not yet been determined . We sought to evaluate the outcome and adverse effects in patients with advanced stage endometrial cancer treated with postoperative chemotherapy and radiation  to determine whether there was an advantage to a particular sequencing modality . METHODS A multicenter retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1993 to 2007 was conducted . Inclusion criteria were comprehensive staging procedure including  hysterectomy  ,  bilateral salpingo-oophorectomy  ,  + /- selective pelvic/aortic lymphadenectomy , and treatment with adjuvant chemotherapy and radiation . Differences in frequencies of adverse events were tested with Pearson 's chi-square test for comparing proportions . OS and PFS rates were calculated using Kaplan-Meier estimates . Hazard Ratios ( HR ) were estimated from multivariate Cox proportional hazards models . RESULTS One hundred and nine patients with advanced stage endometrial cancer were identified who received  postoperative adjuvant therapies ; 41 % ( n=45 ) chemotherapy followed by radiation and then further chemotherapy ( CRC ) , 17 % ( n=18 ) radiation followed by chemotherapy ( RC ) , and 42 % ( n=46 ) chemotherapy followed by radiation ( CR ) . The median age was 62 years ( range : 35 - 83 ) ; 48 % had endometrioid tumors ; and 90 % underwent optimal cytoreduction . There was no difference in the frequency of adverse effects due to either chemotherapy ( p=0.35 ) or radiotherapy ( p=0.14 ) ; dose modifications ( p=0.055 ) ; or delays ( p=0.80 ) between the various sequencing modalities . There was a significant difference between adjuvant treatment groups for both OS ( log rank p=0.011 ) and PFS ( log rank p=0.025 ) , with those receiving CRC having a superior 3-year OS ( 88 % ) and PFS ( 69 % ) compared to RC ( 54 % and 47 % ) or CR ( 57 % and 52 % ) . After adjusting for stage , age , grade , race , histology and cytoreduction status the OS HR for therapy was 5.74 ( 95 % CI , 1.96 to 16.77 ) for RC and 2.60 ( 95 % CI , 1.01 to 6.71 ) for CR , compared to CRC , p=0.003 . When the analysis was restricted to optimally cytoreduced patients , those who were treated with RC were at higher risk for disease progression [ HR=3.53 ( 95 % CI , 1.29 to 9.71 ) ] , p=0.024 , and death [ HR=7.24 ( 95 % CI , 2.25 to 23.37 ) ] , p=0.001 , than patients who received sequential CRC . CONCLUSIONS Sequential CRC was associated with improved survival in women with advanced stage disease compared to other sequencing modalities with a similar adverse effect profile . Future clinical trials are needed to prospect ively evaluate appropriate sequencing and types of adjuvant chemotherapy and radiotherapy for the treatment of advanced stage endometrial cancer Purpose : P-glycoprotein , encoded by the mdr-1 gene , confers multidrug resistance to a variety of antineoplastic agents , e.g. , paclitaxel . Recently , different polymorphisms in the mdr-1 gene have been identified and their consequences for the function of P-glycoprotein , as well as for the treatment response to P-glycoprotein substrates , are being clarified . We analyzed the allelic frequencies at polymorphic sites G2677T/A and C3435 T in ovarian cancer patients with good or poor response to treatment with paclitaxel in combination with carboplatin  in order to evaluate their predictive values . Experimental Design : Fifty-three patients were included in the study ; 28 of them had been relapse-free for at least 1 year and 25 had progressive disease or relapsed within 12 months . A reference material consisting of 200 individuals was also analyzed . The genotypes of each single nucleotide polymorphism ( SNP ) were determined using Pyrosequencing . Results : The G2677T/A SNP was found to significantly correlate with treatment outcome . The probability of responding to paclitaxel treatment was higher in homozygously mutated patients ( T/T or T/A ; Fisher 's exact test ; P < 0.05 ) . The frequency of the T or A alleles was also higher in the group of patients who had a good response ( P < 0.05 ) . There was also a dose-dependent influence of the number of mutated alleles on the response to paclitaxel treatment ( χ2 test for linear-by-linear association ; P = 0.03 ) . However , the C3435 T SNP was not found to correlate to treatment outcome . Conclusions : The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents . In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn ( C→T ) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively . Using the SNapShot assay , we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients . Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy . Although not significant , platinum-resistance was less frequently observed in patients with the C/T+T/T genotype ( P=0.064 ) . Multivariate analysis showed that the C/T+T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer ( odds ratio 0.17 , 95 % confidence interval 0.04 - 0.74 , P=0.018 , Fisher 's exact test ) . No significant correlation was observed between overall survival and the ERCC1 polymorphism . Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients . However , these findings require prospect i ve confirmation LBA1 Background : BEV , a humanized anti-VEGF monoclonal antibody , has demonstrated single-agent activity in patients with recurrent EOC , or PPC . The therapeutic impact of concurrent ± maintenance BEV with st and ard chemotherapy ( CT ) was evaluated in an international , double-blind , placebo-controlled phase III trial . METHODS Eligible patients had newly diagnosed , previously untreated EOC , PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking ; stage III ( macroscopic residual disease ) or stage IV disease . The r and omly allocated regimens were ( 1 ) CT ( IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1 - 6 ) + placebo cycles (C)2 - 22 ( R1 ) ( 2 ) CT + concurrent BEV ( 15 mg/kg ) C2 - 6 + placebo C7 - 22 ( R2 ) ( 3 ) CT + concurrent BEV C2 - 6 + maintenance BEV C7 - 22 ( R3 ) Infusions were administered d1 of a 21d cycle . The primary endpoint is progression-free survival ( PFS ) ( radiographic , CA125 , clinical criteria or death ) ; secondary endpoints include overall survival , safety , and QoL.  RESULTS 1,873 patients , median age 60 , were enrolled from 9/05 - 6/09 . Stage III optimally debulked ( 34 % ) , stage III sub-optimally debulked ( 40 % ) , and stage IV ( 26 % ) patients were similarly distributed in each treatment group . Grade 3 - 4 hypertension was reported in 1.6 % ( R1 ) , 5.4 % ( R2 ) , and 10.0 % ( R3 ) . Grade ≥ 3 GI perforation , hemorrhage or fistula occurred in 0.8 % ( R1 ) , 2.6 % ( R2 ) and 2.3 % ( R3 ) . Relative to R1 , the hazard of first progression or death for R2 was 0.908 ( 95 % CI : 0.795 - 1.04 , p=0.16 ) and for R3 was 0.717 ( 95 % CI : 0.625 - 0.824 , p<0.0001 ) . CONCLUSIONS This study demonstrates that front-line treatment of EOC , PPC , and FTC patients  with CT plus concurrent and maintenance BEV  prolongs PFS . This is the first anti-angiogenic agent to demonstrate benefit in this population . [ Table : see text ] OBJECTIVE Interleukin 1 ( IL-1 ) and IL-10 are critically involved in tumorigenesis . We investigated polymorphisms of IL-1 and IL-10 genes in patients with ovarian cancer ( OC ) . METHODS In a prospect i ve , case-control study 147 patients with OC and 129 patients without history of any malignancy ( CG ) were genotyped for IL-1 gene ( IL-1alpha -889 T/C and IL-1beta -511 C/T ) and IL-10 gene ( IL-10 -1082 G/A , -819 C/T and -592 C/A ) using pyrosequencing . RESULTS IL-10 polymorphisms in -819 and -592 positions correlated with the postoperative residual tumor mass ( p=0.036 and p=0.035 , respectively ) . The chance of achieving optimal tumor debulking was 1.49 times greater for patients with the C/C genotype at -819 and -512 positions than for patients with other genotypes . There were no significant associations between allelic frequencies for IL-1alpha and IL-1beta in OC . IL-10 -819 CC and -592 CC genotypes were associated in univariate analysis with a better disease-free and overall survival . CONCLUSIONS IL-10 promoter polymorphism may be related with the ability to achieve optimal tumor debulking . Polymorphism in IL-10 gene seems to influence the overall and disease-free survival rate . Subsequent multi-institutional studies with high number of patients are warranted to confirm these results 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 
    Output:
    
No consistent association between any gene polymorphism and clinical outcome in gynecological cancers has been found across studies .