Association of Hypoxia-Inducible Factor 1-Alpha Gene Polymorphisms and Colorectal Cancer Prognosis.

BACKGROUND:Hypoxia inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Recently, two single nucleotide polymorphisms (SNPs) in the HIF-1 alpha gene, C1772T and G1790A, were shown to cause significantly higher transcriptional activity than did the wild-type. This study aimed to investigate the effect of these SNPs on the prognosis of colorectal cancer (CRC).PATIENTS AND METHODS:DNA from 336 CRC patients was genotyped. Genotypes of each polymorphism were tested for association with disease-free survival (DFS) using univariate and multivariate Cox-regression analysis.RESULTS:Genotype frequencies were: CC 75.6%, CT 18.8% and TT 1.8% for HIF1A1 C1772T and GG 93.2%, GA 2.7% and AA 0% for G1790A. A statistically significant association between DFS and clinicopathological features was observed. However, no association was found between HIF1A1 C1772T (p=0.44; risk ratio of recurrence, RR=1.19, 95% confidence interval, CI=0.77 to 1.83) and G1790A (p=0.89; RR=0.92, 95% CI=0.29 to 2.90) polymorphisms and DFS in univariate and multivariate Cox-regression analysis.CONCLUSION:These results suggest that HIF1A1 C1772T and G1790A polymorphisms are not involved in the progression or metastasis of CRC.