Abstract
INTRODUCTION: Previous studies have reported the impact of the hypoxia inducible factor-1α (HIF1α) gene on risk of renal cell carcinoma (RCC). However, the results of these previous studies were inconsistent. Hence, this study aimed to verify the influence of single-nucleotide polymorphisms (SNPs) in the HIF1α gene and their interaction with environmental factors on RCC risk. METHODS: PCR-based restriction fragment length polymorphism was used to genotype four SNPs. Logistic regression was utilized to test the association between HIF1α SNPs and RCC risk. A generalized multifactor dimensionality reduction model was employed to evaluate the potential interaction of the four SNPs in the HIF1α gene with environmental factors. RESULTS: The rs11549465-CT, rs11549465-TT, and rs11549465-CT+TT genotypes were all associated with increased risk of RCC; the adjusted ORs (95% CI) were 1.74 (1.38-2.12) (CT vs. CC), 1.93 (1.47-2.43) (TT vs. CC), and 1.78 (1.41-2.18) (CT+TT vs. CC), respectively. We also found that the rs11549467-GA and rs11549467-GA+AA genotypes were associated with increased RCC risk, and adjusted ORs (95% CI) were 1.81 (1.49-2.16) (GA vs. GG), 1.79 (1.47-2.13) (GA+AA vs. GG), respectively. We found a statistically significant combination (including rs11549465 and smoking). Compared to non-smokers with the rs11549465-CC genotype, current or ever smokers with rs11549465-CT+TT genotype had the highest RCC risk; the OR (95% CI) was 3.68 (1.97-5.41). CONCLUSION: This study demonstrated a significant impact of HIF1α polymorphisms on RCC risk. Additionally, this impact could be influenced by environmental factors, such as smoking status.