TNF-α -857C>T Genotype is Predictive of Clinical Response after Treatment with Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma

Abstract

Background: Genotypes of tumor necrosis factor alpha (TNF-α) and its surface receptors, TNFRSF1A and TNFRSF1B, have been examined in terms of the progression, metastasis, clinical efficacy, and prognosis of various cancers; however, little is known about their effects on clinical outcome in patients with esophageal squamous cell carcinoma (ESCC). In this study, TNF-α and TNFRSF1A genotypes were retrospectively evaluated in terms of predicting clinical response, long-term survival, and severe acute toxicities in 46 male Japanese ESCC patients treated with definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT).Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course being repeated after a 2-week interval. The TNF-α -1031T>C (rs1799964), -863C>A (rs1800630), -857C>T (rs1799724), -308G>A (rs1800629), -238G>A (rs361525), TNFRSF1A -609G>T (rs4149570), and 36A>G (rs767455) genotypes were evaluated.Results: The TNF-α -857C>T genotype was found to be predictive of clinical response, i.e., complete response or not (P = 0.010, Fisher's exact test), but had no effect on long-term survival (CC-857 vs. CT-857 + TT-857, P = 0.072, Fisher's exact test, P = 0.070, Log-rank test).Conclusions: The TNF-α -857C>T genotype was found to be predictive of clinical response and was more likely to predict long-term survival in Japanese ESCC patients receiving definitive 5-FU/CDDP-based CRT. Further clinical investigations with a larger number of patients or experiments in vitro should be performed to assess the predictive value of this genotype following CRT.

TNFR1single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulatein situcervical TNFR1 expression

“…No association was found between TNFR1 rs2234649 and gastric mucosa-associated lymphoid tissue lymphoma [24], and in myelopathy associated to HTLV-1 infection [37]. However, controversial results were found in TNFR1 rs767455 SNPs, where no association was described in esophageal squamous cell carcinoma [23], while a significant increased risk for breast cancer [38, 39] and odontogenic keratocystic tumor [40] were observed. Moreover, others TNFR1 SNPs have been described in different cancer types.…”

“…This receptor is the main mediator of TNF signaling pathways, affecting the binding of TNF-α in the membrane [17]. A growing number of genetic studies have identified several single nucleotide polymorphisms (SNPs) in the TNFR1A gene as susceptibility or predictive markers of multifactorial inflammatory disorders [18–22] and cancer [23–28]. One of the functional consequences of these variants could be linked to regulation of gene expression [29].…”

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

“…Tumor necrosis factor alpha was known as a cytokine that could kill cancer cells; however, sometimes it can cause the reproduction, invasion, and metastasis of cancer cells (25). Therefore, elevated TNF-α levels may have deleterious outcomes.…”

TNFRSF1A Gene Polymorphism (−610 T > G, rs4149570) as a Predictor of Malnutrition and a Prognostic Factor in Patients Subjected to Intensity-Modulated Radiation Therapy Due to Head and Neck Cancer

“…TNF-α activates signals for pathways starting within two receptors: tumor necrosis factor receptor superfamily member 1A (TNFRSF1A (CD120a) and TNFRSF1B (CD120b) [ 12 , 13 , 14 ]. It plays a critical role in non-lysosomal and lysosomal proteolytic pathways, induction of the ubiquitin-proteasome pathway, decrease in protein synthesis, decrease in adipose tissue enzymes (e.g., lipoprotein-lipase), and simultaneous increase in adipose tissue lipolysis [ 7 ].…”