Tumour necrosis factor alpha 308 G/A is a risk marker for the progression from high-grade lesions to invasive cervical cancer

Abstract

Tumour necrosis factor alpha (TNF-α) is a strong pro-inflammatory cytokine with important functions on immune response to viral infections. A single nucleotide polymorphism on the -308 position of the promoter region of TNFA gene characterised by a G > A transition has been associated with different TNF-α levels and therefore with differential susceptibility for the development several diseases. A cross-sectional case-control study was performed with 509 women with cancer from the northern region of Portugal, including 205 healthy women and 337 women with different cervical lesions including invasive cervical. The -308G > A polymorphism genotyping was performed with TaqMan® SNP Genotyping Assay and studied for its association with cervical cancer development. This study showed increased frequency of the -308A allele in women with any cervical lesions. Statistical analysis revealed that -308A carriers are associated with an almost 2-fold increased risk for invasive cervical cancer development (p = 0.005; odds ratio (OR) = 1.87). Similar results were found when comparing the risk of progression between preinvasive lesions and invasive cervical cancer development (p = 0.002; OR = 2.41). Our results reveal that -308 TNFA AA individuals are at increased risk of invasive cervical cancer development and more important, that the risk is significantly increased for the progression from premalignant lesion to invasive cancer. Considering previous data and this study, this polymorphism confirms to be a significant marker in our population.