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

Abstract

Background: Malnutrition is a nutritional disorder observed in 52% of patients with head and neck cancer (HNC). Malnutrition is frequently related to the increased level of proinflammatory cytokines. In turn, ongoing inflammation is associated with increased catabolism of skeletal muscle and lipolysis. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that plays a pivotal role in the development of malnutrition and cachexia in cancer patients. The aim of the study was to assess the relationship between a functional single-nucleotide polymorphism (SNP) −610 T > G (rs4149570) of the TNFRSF1A gene and the occurrence of nutritional disorders in patients subjected to RT due to HNC. Methods: The study group consisted of 77 patients with HNC treated at the Oncology Department of the Medical University in Lublin. Genotyping of the TNFRSF1A gene was performed using capillary electrophoresis (Genetic Analyzer 3500). Results: Multivariable analysis revealed that the TT genotype of the TNFRSF1A gene (−610 T > G) was an independent predictor of severe malnutrition (odds ratio—OR = 5.05; p = 0.0350). Moreover, the TT genotype of this gene was independently related to a higher risk of critical weight loss (CWL) (OR = 24.85; p = 0.0009). Conclusions: SNP (−610 T > G) of the TNFRSF1A may be a useful marker in the assessment of the risk of nutritional deficiencies in HNC patients treated with intensity-modulated radiotherapy (IMRT).

TNF-α-1031T/C gene polymorphism as a predictor of malnutrition in patients with gastric cancer

“…Sharma et al found that TNF-α -238 AA and -308 AA genotype in patients with end-stage renal disease exhibited a higher susceptibility to malnutrition and higher levels of TNF-α ( 31 ). Homa-Mlak et al investigated the association between single nucleotide polymorphisms in the TNF-α-610 T > G (rs4149570) gene and the development of malnutrition in HNC patients receiving radiotherapy ( 23 ). They found that the TT genotype possessed a higher risk of malnutrition (OR = 5.05; p = 0.0350) and was also associated with critical weight loss (OR = 24.85; p = 0.0009).…”

“…As SNPs do not change during the disease process, in addition, the risk of malnutrition is individual and does not appear to be related to demographic or most clinical factors. Therefore, it has been proposed that the risk of malnutrition may be related to genetic predisposition ( 23 , 24 ). TNF-α is probably the most characteristic cytokine in malnutrition.…”

“…In addition to lipid and muscle wasting, elevated TNF-α can lead to anorexia, activate skeletal muscle protein degradation, inhibit protein synthesis, induce insulin resistance and mediate systemic inflammation in cancer malnutrition, further exacerbating malnutrition ( 29 ). Several polymorphisms within the TNF-α promoter region (-238, -244, -308, -376, -489, -575, -610, -851, -857, -863, -1031) have been reported to affect the expression of TNF-α genes and disease susceptibility ( 23 , 25 , 30–36 ). The most recent of these studies demonstrated that the TNF-α-1031T/C SNP (rs1799964) may be associated with malnutrition ( 25 , 33 ).…”

“…The causes of cancer malnutrition are not fully understood, and the role of cancer-inducing inflammatory cytokines such as IL-6 and TNF-α in its occurrence and development is gradually being recognized (20,21). Meanwhile, an increasing number of studies have confirmed that cytokine levels in the human organism are regulated by host genes and that cytokine gene polymorphic sequences may be genetic markers of susceptibility or clinical manifestations of certain infectious diseases (22). As SNPs do not change during the disease process, in addition, the risk of malnutrition is individual and does not appear to be related to demographic or most clinical factors.…”