Genetic variations in angiogenesis-related genes lead to marked differences among patients in how well they respond to drugs that block new blood vessel formation. In a study of 57 individuals with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, researchers tested 20 single nucleotide polymorphisms (SNPs) in 13 genes from the angiogenesis pathway to find markers that could forecast tumor shrinkage, progression-free survival (PFS), and overall survival (OS). DNA was obtained from archived formalin-fixed paraffin-embedded tumor tissue and genotyped with the iPLEX® Assay. Patients carrying the variant allele of CD39 rs11188513 were significantly more likely to achieve a good tumor response (p = 0.024). Those with two copies of the common (wild-type) allele at FGF2 rs1960669 had a median PFS of 10.95 months, whereas patients with at least one rare A allele had a median PFS of only 5.44 months (hazard ratio 3.30, 95% CI 1.52–7.14, p = 0.001). Having two common alleles at either MMP9 rs2236416 or MMP9 rs2274755 was linked to longer PFS (median 9.48 months for both) compared with 6.00 and 6.62 months, respectively, in patients carrying at least one rare allele (p = 0.022 and p = 0.043). Median overall survival reached 30.92 months in patients homozygous for the common allele of ANGPT1 rs2445365 versus 22.07 months in those with at least one rare A allele (p = 0.034).
These polymorphisms in angiogenesis pathway genes appear useful for predicting both treatment response and survival in metastatic colorectal cancer patients receiving bevacizumab-based therapy.
