-308 G/A TNF-α gene polymorphism influences the course of basal cell carcinoma in a Polish population

Abstract

Introduction: The etiopathogenesis of basal cell carcinoma (BCC) is multifactorial. The TNF-α gene seems to be an interesting gene candidate for BCC susceptibility because of the proinflammatory and immunosuppressive properties of its product. The aim of the study was to assess the frequency of -308 G/A and -238 G/A gene polymorphisms in the TNF-α gene and serum levels of cytokine in patients with BCC.

Material and methods: The study included 176 (94 women, 82 men) patients with BCC and 261 healthy volunteers. -308 G/A and -238 G/A TNF-α polymorphisms were analyzed using the amplification refractory mutation system-polymerase chain reaction method (ARMS-PCR). Serum concentrations of TNF-α were measured using ELISA.

Results: There was no statistically significant association between allele, genotype and haplotype frequencies in BCC patients in comparison with controls. Occurrence of the -308 TNF-α A allele or GA genotype in the group of patients with BCC increases risk of recurrence of tumor recurrence (OR = 4.8, 95% CI: 1.6-13.9, p = 0.004 and OR = 4.97, 95% CI: 1.7-14.5, p = 0.004). Moreover, -308 TNF-α GG genotype decreased risk of recurrence (OR = 0.2, 95% CI: 0.07-0.6, p = 0.004). The -238/-308 GA haplotype was connected with increased risk of recurrence (OR = 4.36, 95% CI: 1.49-12.7, p = 0.007). We also found significantly higher TNF-α levels among BCC patients in comparison with controls (p = 0.004).

Conclusions: The obtained results did not confirm the role of the -308 G/A and -238 G/A TNF-α gene polymorphisms in BCC development, but the presence of the A allele or GA genotype in -308 G/A TNF-α gene polymorphism may have an impact on the course of the disease.

Keywords: TNF-α; basal cell carcinoma; gene polymorphism; tumor necrosis factor α.

Figure 1

Allele frequencies of –308 G/A TNF polymorphism in BCC patients with and without tumor recurrence (p = 0.005)

Figure 2

Genotype frequencies of –308 G/A TNF polymorphism in BCC patients with and without tumor recurrence

Figure 3

–238/–308 TNF diplotype frequencies in BCC patients with and without tumor recurrence

Figure 4

–238/–308 TNF haplotype frequencies in BCC patients with and without tumor recurrence

Figure 5

TNF-α serum level among BCC patients in comparison with healthy controls (p = 0.004)