Association of Interleukin-12A Genotypes With Nasopharyngeal Carcinoma Risk.

BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC) is a virally associated epithelial malignancy with a high prevalence in East Asia. While Epstein-Barr virus (EBV) infection is a well-established risk factor, the role of host immune-related genetic variants remains insufficiently understood. Interleukin-12 (IL-12), a key immunoregulatory cytokine, is essential for EBV-specific T-cell responses, however, the impact of IL-12A gene polymorphisms on NPC susceptibility remains unknown. MATERIALS AND METHODS: This case-control study investigated the association between IL-12A rs568408 and rs2243115 genotypes and NPC risk in a Taiwanese population comprising 208 patients with NPC and 416 matched cancer-free controls. Genotype and allele frequencies were assessed, and gene-lifestyle interactions were evaluated based on smoking, alcohol consumption, and betel quid chewing. RESULTS: No significant associations were observed between either IL-12A rs568408 or rs2243115 genotypes and overall NPC risk (p for trend=0.5286 and 0.4910). However, stratified analysis revealed that the rs568408 AA variant genotype conferred significantly elevated NPC risk among smokers [odds ratio (OR)=5.47, 95% confidence interval (95%CI)=1.03-29.05, p=0.0397], and the AG variant genotype conferred significantly elevated NPC risk among betel quid users (OR=2.61, 95%CI=1.32-5.14, p=0.0080). In contrast, no significant associations were observed among non-smokers, non-betel quid chewers, alcohol drinkers, or non-alcohol drinkers (all p>0.05). No any significant interaction was found for rs2243115 genotypes. CONCLUSION: IL-12A rs568408 may interact with tobacco and betel quid exposures to influence NPC susceptibility. These findings highlight the importance of integrating genetic and environmental factors in NPC risk assessment and warrant further validation in larger, multi-ethnic NPC cohorts.