Impact of hypoxia-inducible factor-1α (HIF1α) gene polymorphisms on renal cell carcinoma susceptibility in a Chinese Han population

Objective: Previous studies have reported the impact of 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) of the HIF1α gene and their interaction with environmental factors on RCC risk. Methods: PCR-based restriction fragment length polymorphism was used for four SNP genotyping. Logistic regression was utilized to test the association between HIF-1α gene SNPs and RCC risk. Generalized multifactor dimensionality reduction (GMDR) model was employed to evaluate the potential interaction of the four SNPs of the HIF-1α gene with environmental factors. Results: Both the rs11549465- CT, rs11549465- TT and rs11549465- CT+TT genotype 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 with non-smokers with 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). Conclusions This study demonstrated a significant impact of HIF-1α polymorphisms on RCC risk. Additionally, this impact could be influenced by environmental factors, such as smoking status.