Abstract Objectives The WD repeat domain 74 ( WDR74 ) gene is crucial for ribosome biogenesis and has been implicated in various tumors; however, the impact of its genetic variation on Esophageal Cancer (ESCA) remains unclear. This study aims to investigate the association between WDR74 (WD repeat domain 74) rs11231247 polymorphism and the susceptibility to esophageal cancer (ESCA). Methods We conducted a case-control study comprising 480 newly diagnosed ESCA patients and 480 healthy controls recruited during the same period. Genotyping of WDR74 rs11231247 was performed using chain reaction-restriction fragment length polymorphism (PCR-RFLP). Non-conditional logistic regression models were used to estimate the association between WDR74 polymorphism and the susceptibility to ESCA. Additionally, bioinformatics analyses were performed using the online tools GEPIA, TNMplot, EWAS Data Hub, MethPrimer, and Pancan-meQTL to explore gene expression and methylation patterns. Results Bioinformatic analysis revealed that WDR74 expression was significantly upregulated in ESCA tissues compared to adjacent normal tissues and varied significantly by pathological stage (p<0.05). Furthermore, hypomethylation at the cg15676512 site was associated with improved patient survival. The case-control analysis demonstrated that the rs11231247 CC genotype was associated with a significantly lower risk of developing ESCA (OR=0.201, 95 % CI: 0.044–0.981, p=0.047). Stratified analysis indicated that the protective effect of the C allele was specifically significant in males (OR=0.676, 95 % CI: 0.461–0.991, p=0.045), but not in females. Conclusions The WDR74 rs11231247 polymorphism is associated with ESCA susceptibility. Specifically, the C allele confers a protective effect against ESCA, particularly in males. These findings, supported by bioinformatic evidence, suggest a potential functional role for WDR74 in esophageal carcinogenesis.
Wu et al. (Wed,) studied this question.