Interaction between tumour necrosis factor-α gene polymorphisms and substance use on risk of betel quid-related oral and pharyngeal squamous cell carcinoma in Taiwan

Abstract

ObjectiveBetel quid (BQ) components induce the secretion of tumour necrosis factor-alpha (TNF-α) in oral keratinocytes, which promotes oral mucosal inflammation and oral cancer. This study was carried out to evaluate the association of TNFA genetic variants (−308G>A and −238G>A) with the risk and prognosis of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC). DesignA total of 403 subjects (205 cancer cases and 198 healthy controls) who habitually chewed BQ were recruited. The genotypes were determined by TaqMan real-time assays. ResultsG allele and G/G genotype at TNFA −308 were associated with a 1.95-fold (95%CI: 1.16–3.28, pcorrected=0.024) and 2.28-fold (95%CI: 1.30–4.00, pcorrected=0.008) increased risk of cancer as compared to those with A allele or A/A+A/G genotypes, respectively. In addition, G allele (p=0.080) and G/G genotype (p=0.076) at TNFA −238 were associated with a borderline but statistically significant increased risk of OPSCC. The combined G/G+G/G genotype at both loci had a 2.37-fold increased risk of OPSCC as compared to those with other combined genotypes (95%CI: 1.41–4.00, p=0.001). Interactions between combined genotypes and smoking status were also found to contribute to risk of BQ-related OPSCC. There was no association of TNFA genotypes with clinicopathologic findings or the survival of OPSCC patients. ConclusionsBQ-chewers who carry the G allele or G/G genotype in TNFA −308 may have an increased risk of OPSCC. The intensity of cigarette smoking modulates the effect of the combined TNFA genotypes on risk of BQ-related OPSCC.