Both alpha-enolase and myc promoter-binding protein-1 (MBP-1) originate from a single gene ENO1 through alternative translational starting sites.Alpha-enolase is a glycolytic enzyme that catalyzes the formation ofphosphoenol pyruvate in the cell cytoplasm, which is a main target gene of HIF-1 in the hypoxia pathway in solid tumor progression,whereas MBP-1 binds to the P2 c-myc promoter and competes with the TATA box binding protein (TBP) to suppress gene transcription.Therefore, genetic variants in ENO1 may affect cancer susceptibility and progression associated with hypoxia.In this case-control study, we evaluated associations between three selected potentially functional single nucleotide polymorphisms (SNPs) (rs3820037A＞G, rs4908519C＞T and rs2274971C＞T) in ENO 1 and risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,084 non-Hispanic white patients and 1,120 cancer-free controls.We found that the rs3820037 and rs4908519 variant genotypes were associated with marginally significantly decreased SCCHN risk (OR =0.85, 95％ CI 0.71-1.02 for rs3820037 and OR =0.83, 95％ CI 0.69-1.01 for rs4908519), compared with the homozygous wild genotypes.However, there showed significant joint effects of variant alleles ofrs3820037G and rs4908519T in combined analysis and haplotype analysis.In 270 Epstein-Barr virus-transformed lymphoblastoid cell lines derived from healthy individuals, ENO1 mRNA expression was significantly lower for the genotypes of variant rs3820037G and rs4908519T in a dominant model.Furthermore, a significant protective effect was found in tumor progression for rs3820037 in dominant model (OR =0.74, 95％ CI 0.57-0.97).These results suggest that these genetic variants in ENO1 may be functional and thus contribute to SCCHN susceptibility and tumor progression.However, our findings need to be replicated in further large epidemiological and functional studies.