PURPOSE: There is substantial germline genetic variability within angiogenesis 
pathway genes, thereby causing interindividual differences in angiogenic 
capacity and resistance to antiangiogenesis therapy. We investigated germline 
polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis 
pathways to predict clinical outcome and tumor response in metastatic colorectal 
cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based 
chemotherapy.
EXPERIMENTAL DESIGN: A total of 132 patients treated with first-line bevacizumab 
and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from 
whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the 
study were progression-free survival (PFS), overall survival (OS), and response 
rate (RR).
RESULTS: The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were 
associated with increased OS and remained significant in multivariate Cox 
regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 
0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of 
HIF1α rs11549465 C>T was significantly associated with increased PFS but lost 
its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 
T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, 
with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 
0.003).
CONCLUSION: In this study, we identified common germline variants in 
VEGF-dependent and -independent angiogenesis genes predicting clinical outcome 
and tumor response in patients with mCRC receiving first-line bevacizumab and 
oxaliplatin-based chemotherapy.