Interaction Analysis of SHMT1/2 Gene Variants with HCC in Chinese Patients

Abstract

Background: Metabolic reprogramming caused by SHMT1/2, as key enzymes in one-carbon metabolism, has been considered to play a critical role in occurrence and progression of hepatocellular carcinoma (HCC). However, the associations between single nucleotide polymorphisms (SNPs) in SHMT1/2 genes and susceptibility of HCC remains unknown. The purpose of this study was to investigate the relation between four candidate SNPs in SHMT1/2 and risk of HCC in Chinese population. Materials and methods: A case-control study including 514 HCC patients and 234 controls was performed to determine associations between SNPs of SHMT1/2 and HCC risk,isolated via mass spectrometry. Results: Our data revealed that SHMT2 rs2229717 was significantly associated with HCC risk when compared to healthy controls under multiple genetic models (Allele T: odds ratio (OR) = 0.73, P=0.023; Dominant Model: OR = 0.72, P=0.044). When our cohort was stratified by sex, male subjects with the T allele and TT genotype for rs2229717 exhibited a decreased risk for HCC risk (OR=0.67, 95%CI=0.50-0.91; OR=0.43, 95%CI=0.18-0.99). In addition, after age stratification was executed, the results showed that both the T allele and the GT genotype for rs2229717 were less common in HCC patients under 50 years old. Conclusion: These data indicate that rs2229717is a predisposing factor for HCC and may affect the occurrence of HCC in various age or sex subgroups, suggesting that SHMT2 rs2229717may be as a useful predictive or diagnostic tool for HCC in some populations.