BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. More advanced work is required in the detection of biomarkers for CRC susceptibility and prognosis. High-mobility group box-1 (HMGB1) is an angiogenesis-related gene reported to be associated with the development of CRC. The direct evidence of HMGB1 gene polymorphisms as biomarkers for CRC has not been reported previously.Material/MethodsA total of 240 CRC patients and 480 healthy controls were periodically enrolled. DNA was extracted from blood specimens. The distributions of SNPs of HMGB1 were determined by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay.ResultsIn this case-control study, we observed a significant association between overall CRC risk and SNP rs2249825 (CG vs. CC and GG vs. CC). Participants carrying both rs2249825 CG (OR, 2.67; 95% CI, 1.89 to 3.78) and rs2249825 GG genotypes (OR, 2.32; 95% CI, 1.13 to 4.73) had a significantly increased risk of developing CRC compared to those carrying GG genotype. rs2249825 was associated with the risk of CRC in the dominant model but not in the recessive model. However, we found no significant differences in the rs1412125 or rs1045411 polymorphisms in the HMGB1. Advanced analyses showed that the number of rs2249825 G alleles showed a significant relationship with risk of CRC.ConclusionsOur results show an association between HMGB1 rs2249825 SNP and CRC incidence in the Chinese Han population. However, population-based studies with more subjects and prognostic effects are needed to verify the association of HMGB1 SNPs with CRC susceptibility, severity, and long-term prognosis.