Polymorphisms in the @entity7 ( @entity7 )/angiogenesis pathway have been implicated previously in @entity5 risk, prognosis and response to therapy including in @entity420 . Prior @entity420 studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new @entity7 pathway polymorphisms associated with @entity420 prognosis and validated them in an independent cohort of @entity420 @entity1 . In 231 @entity420 @entity1 of all stages/treatment plans, 58 genetic polymorphisms (18 @entity319 , 7 @entity7 and 33 @entity6758 ) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with @entity1349 ( @entity1349 ) and @entity1349 ( @entity1349 ). Significantly associated polymorphisms were then validated in an independent cohort of 137 @entity420 @entity1 . Among the 231 discovery cohort @entity1 , 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median @entity1349 and @entity1349 were 20 and 12 months, respectively. @entity319 @entity69256 was found significantly associated with @entity1349 (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). @entity6758 @entity69257 and @entity69258 were significantly associated with @entity1349 (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No @entity7 polymorphisms were found significantly associated with either outcome. Upon validation, @entity6758 @entity69257 remained strongly associated with @entity1349 (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). @entity6758 @entity69257 is significantly associated with @entity1349 in @entity420 , whereby each variant allele confers a 45-60% increased risk of mortality. Validation and evaluation of this association in other @entity5 sites are warranted.

Discovery and validation of @entity7 ( XXXX ) pathway polymorphisms in @entity420 outcome.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor', 'VEGF', 'VEGFA'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity69257 :: ('rs3794405', 'SNP') :: ['rs3794405'] @entity319 :: ('3791', 'Gene') :: ['KDR'] @entity69256 :: ('rs17709898', 'SNP') :: ['rs17709898'] @entity6758 :: ('2321', 'Gene') :: ['FLT1'] @entity69258 :: ('rs678714', 'SNP') :: ['rs678714'] @entity420 :: ('MESH:D000230', 'Disease') :: ['esophageal adenocarcinoma'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'PFS', 'overall survival', 'progression-free survival']
@entity7 :: (7422,Gene) :: ['VEGF']
