Contribution of Interleukin-4 Promoter Genotypes to Gastric Cancer Risk in Taiwan.

Background/aim: Gastric adenocarcinoma (GACA) remains a major global health concern, particularly in Asia, due to its poor prognosis and complex etiology. The interaction between genetic factors and environmental exposures, such as smoking, alcohol consumption, and Helicobacter pylori (HP) infection, plays a crucial role in GACA risk.

Materials and methods: Interleukin-4 (IL-4) gene promoter polymorphic rs2243248 (T-1099G), rs2243250 (C-589T), and rs2070874 (C-33T) genotypes were analyzed in 161 GACA patients and 483 non-cancer control subjects from a Taiwanese population by PCR-RFLP methodology. The gene-environment interactions were evaluated by stratified analysis.

Results: Genotypic analysis revealed no significant association between IL-4 polymorphisms and GACA risk (all p>0.05). However, interactions between IL-4 C-589T and C-33T genotypes with HP infection were observed (p=0.0114 and 0.0009). In addition, T-1099G and C-33T genotypes interacted with alcohol consumption (p=0.0346 and 0.0295). T-1099G and C-589T variant genotypes were associated with an increased risk of metastasis (p=0.0313 and 0.0118). Moreover, IL-4 polymorphisms did not correlate with smoking behavior in influencing GACA susceptibility.

Conclusion: While IL-4 polymorphisms alone are not predictors of GACA risk, their interactions with environmental factors may contribute to the progression of the disease. Our study emphasizes the need for further research to explore the clinical implications of IL-4 genetic variants in diverse populations and their role in GACA progression.