Association of −308 TNF-α promoter polymorphism with clinical aggressiveness in patients with head and neck squamous cell carcinoma

Abstract

Genetic polymorphisms in the promoter region of the tumour necrosis factor-α (TNF-α) gene are involved in the regulation of the expression levels of its cytokine. Besides, these polymorphisms have been associated with the clinical behaviour of cancer. We investigated the -308 promoter region polymorphisms of the TNF-α gene and its association with the clinicopathological factors of a head and neck squamous cell carcinoma (HNSCC) sample. Furthermore, we analysed the impact of all the variables on the overall survival of patients. A sample of HNSCC (n=89) was evaluated. Clinicopathological factors and overall survival data were gathered. The TNF-α gene was analysed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data analyses were performed by using bivariate and multivariate statistical tests. Significance was set at p<0.05. HNSCC subjects carrying the A allele (GA/AA) exhibited associations with poor performance status (OR=2.82, p=0.039), lesions located on posterior areas (OR=4.02, p=0.002), and large-size tumours (OR=2.91, p=0.015). Subjects carrying only AA genotype exhibited association with poor performance status (OR=6.667, p=0.007). A worse overall survival was noted in subjects with large tumours (OR=4.87, p=0.005) and locoregional metastatic disease (OR=2.50, p=0.018). Our data suggests that the presence of the A allele/AA haplotype in HNSCC individuals might contribute to the higher clinical aggressiveness of malignant disease.

Functional Promoter -308G>A Variant in Tumor Necrosis Factor α Gene Is Associated with Risk and Progression of Gastric Cancer in a Chinese Population

“…In our study, we also found the TNFA -308G>A polymorphism was associated with clinical aggressiveness such as advanced tumor stage and distant metastasis. Similar observation has also been reported in other study [30]. If confirmed by additional studies, this polymorphism might help to accurately predict the clinical course of gastric cancer.…”

Relationship between TNF-α −1031T/C gene polymorphism, plasma level of TNF-α, and risk of cachexia in head and neck cancer patients

“…Patients with CC genotype had significantly higher risk of early death compared to CT and TT haplotypes [28 vs 38 months (HR = 3.630 [0.612–21.55], p  = 0.013)]. Our results are in accordance with Thiago et al findings concerning AA of TNF-α −308G/A (Corrêaa et al 2011). Perhaps, similarly to other promoter SNPs of TNF-α , −1031T/C is a potential regulator of TNF-α protein expression.…”

“…In another study concerning HNC patients, the AA haplotype of -308 G/A was associated with worse prognosis of the disease, shorter overall survival time and increased aggressiveness of the disease. According to the authors, the unfavorable cancer prognosis can be related to TNF-α protein level (Corrêaa et al 2011). Recent large study performed by Johns et al examined over 100 SNPs within genes related to cancer cachexia, and these molecular alterations were associated with both weight loss and muscle wasting in about 1200 studied individuals.…”

A missense polymorphism (rs11895564, Ala380Thr) of integrin alpha 6 is associated with the development and progression of papillary thyroid carcinoma in Korean population

“…Although we cannot exactly explain the difference effect of the A allele on each clinicopathologic characteristic of PTC, the change of amino acid in the rs11895564 SNP may independently related to each clinical phenotype of PTC. In recent studies, polymorphisms of certain genes, such as v-raf murine sarcoma viral oncogene homolog B1 ( BRAF ), cyclin-dependent kinase inhibitor 1B ( CDKN1B ), cholinergic receptor, nicotinic, alpha 3 ( CHRNA3 ), and tumor necrosis factor ( TNF -α) were associated with progression of cancers [31-35]. Chen et al [34] reported that variant allele of rs1051730 in CHRNA3 gene was associated with larger tumor size at diagnosis of squamous cell carcinoma.…”