Purpose: Disheveled-binding antagonist of beta-catenin 1 (DACT1) is involved in tumorigenesis through influencing cell apoptosis and proliferation. We aimed to investigate the effect of three tag single-nucleotide polymorphisms (SNPs) in DACT1 (rs863091 C>T, rs17832998 C>T, and rs167481 C>T) on the occurrence of gastric cancer (GC), their association with specific clinical characteristics, and consideration of the functional relevance of GC-related SNPs.
Subjects and methods: In this hospital-based case-control study, the genotypes were acquired using the TaqMan-MGB method consisting of 602 cases and 602 controls. DACT1 messenger RNA level was evaluated in 76 paired tumoral and normal tissues using quantitative reverse transcription-polymerase chain reaction. Logistic regression was used to evaluate the associations among the DACT1 SNPs and GC.
Results: We found a significant association between the variant genotypes of rs863091 and decreased risk of GC (TT vs CC: P=0.009, adjusted odds ratio =0.34, 95% confidence interval =0.15-0.77; CT + TT vs CC: P=0.030, adjusted odds ratio =0.74, 95% confidence interval =0.57-0.97). In further stratified analyses, rs863091 variant genotypes were associated with a reduced risk of GC in younger individuals (<60 years) and males. No overall significant association with GC risk was observed in SNP rs17832998 or rs167481. Additionally, we assessed DACT1 messenger RNA levels in GC and found that DACT1 expressions of individuals carrying CT and TT genotypes were much higher than those with CC genotype.
Conclusion: Our findings suggest that the DACT1 rs863091 C>T polymorphism may be associated with a decreased risk of GC in the Chinese Han population and influence DACT1 expression.
Keywords: DACT1; gastric cancer; gene expression; polymorphism.