Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer


Background: Hypoxia-inducible factor 1α (HIF-1α) plays an important role in regulating cell survivaland angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have beenshown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-1α has alsobeen demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotidepolymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectalcancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRCpatients and efficacy of chemotherapy. Materials and
Methods: We genotyped two functional SNPs in HIF1Agene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathologicalparameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regressionmodel and Kaplan Meier curves.
Results: Generally, no significant association was found between these 2 SNPsand clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patientscarrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overallsurvival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval(95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvantchemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carryingAC/CC genotype of rs2301113.
Conclusions: Genetic variations in HIF1A gene may modulate the efficacy ofadjuvant chemotherapy after surgery in CRC patients.