Functional XXXX Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer.

@entity1 @entity73211 @entity4557 @entity73214 @entity7 @entity35887 @entity1149 @entity73213 @entity6758 @entity73212
BACKGROUND: We propose that single-nucleotide polymorphisms (SNPs) in genes of the @entity7 pathway of angiogenesis will associate with survival in @entity1149 ( @entity1149 ) @entity1 . METHODS: Fifty-three SNPs in @entity7 -pathway genes were genotyped in 150 European stage I-III @entity1149 @entity1 and tested for associations with @entity1 survival. Replication was performed in an independent cohort of 142 European stage I-III @entity1 . Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. RESULTS: In the initial cohort, five SNPs associated (q < 0.05) with @entity4557 ( @entity4557 ). The minor alleles of intronic @entity6758 SNPs, @entity73211 and @entity35887 , associated with reduced @entity4557 (hazard ratio [HR] = 1.67 [95% confidence interval, CI, 1.22-2.29] and HR = 1.51 [95% CI, 1.14-2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, @entity73212 and @entity73213 , associated with increased @entity4557 (HR = 0.64 [0.46-0.87] and HR = 0.64 [0.47-0.87], respectively), and the minor allelic variant of @entity73212 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP @entity73214 associated with reduced @entity4557 (HR = 1.65 [95% CI, 1.16-2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of @entity35887 on @entity4557 was confirmed in the replication cohort (HR = 1.69 [0.99-2.89], p = 0.028), and the association was significant in pooled analysis of both cohorts (HR = 1.67 [1.21-2.30], p = 0.0001). CONCLUSIONS: The functional @entity6758 variant @entity35887 is a prognostic determinant of recurrence in stage I-III @entity1149 . Its predictive value should be tested in the adjuvant setting of stage I-III @entity1149 .
