Abstract
BackgroundMalnutrition and cachexia are frequent among head and neck cancer (HNC) patients and these syndromes are associated with both poor quality of life and unfavorable disease prognosis. Unfortunately, there are still no established biomarkers that could predict the development of cachexia. Among potential molecular alterations related to cancer cachexia, there are single-nucleotide polymorphisms (SNPs) within genes encoding pro-inflammatory cytokines such as TNF-α.The aim of the studyTo investigate TNF-α −1031T/C SNP as a risk factor of cachexia in 62 HNC patients subjected to radiotherapy. DNA was isolated from whole blood samples and genotyping was conducted using real-time PCR method by means of TaqMan SNP Genotyping Assay. TNF-alpha Human ELISA Kit was used to determine TNF-α concentration in each extracted plasma sample. Moreover, the relationship between genotype variants of TNF-α and plasma level of TNF-α was examined. Detailed clinical–demographic and nutritional data were collected from each study participant.ResultsCC genotype carriers were at a significantly higher risk of being qualified as cachectic compared with other genotype carriers (p = 0.044; HR = 3.724). Subjects, who carried CC genotype had significantly lower body mass compared to patients with TT and CT genotype (p = 0.045). Moreover, CC individuals had the highest TNF-α plasma level (median 10.70 ± 0.72 pg/mL, p = 0.006) among the studied cases. We also noted, that CC genotype carriers had significantly higher risk of early death incidence compared to other genotype carriers [overall survival (OS): 28 vs 38 months (HR = 3.630, p = 0.013)].ConclusionDespite the differences between SGA and NRS scoring, the presence of CC genotype could be a useful objective marker allowing for the prediction of cachexia development in both parenterally nourished and non-parenterally nourished patients. Patients with CC genotype had also the highest risk of early death incidence; therefore, such individuals should be qualified for parenteral nutrition and supportive care at the time of diagnosis to improve further therapy outcomes. Moreover, this is the first study demonstrating the relationship between TNF-α −1031T/C polymorphism and plasma level of TNF-α. This is also the first paper investigating the role of TNF-α −1031T/C in cancer cachexia.
Highlights
The majority of head and neck cancers (HNC) represent a heterogeneous group of squamous-cell-type tumors located in the area of upper aerodigestive tract mucosa.HNC is the sixth most common cancer worldwide with approximately 600,000 new cases diagnosed annually resulting in more than 350,000 deaths every year (Siegel et al 2016; Sanderson and Ironside 2002)
We found that patients with performance status (PS) score greater than or equal to 1 point according to ECOG–WHO scale who simultaneously demonstrated weight loss of at least 5% of total body mass (BM) or carried CC genotype had higher risk of being assessed as cachectic compared to other cases (p = 0.019; Odds ratio (OR) = 3.724 and p = 0.044; OR = 9.737, respectively)
We divided patients into two groups regarding the use of parenteral nutrition intervention [parenterally nourished patients (PN) and patients without parenteral nutrition (WPN)], and we compared the distribution of nutritional and genetic factors between the studied cases
Summary
The majority of head and neck cancers (HNC) represent a heterogeneous group of squamous-cell-type tumors located in the area of upper aerodigestive tract mucosa.HNC is the sixth most common cancer worldwide with approximately 600,000 new cases diagnosed annually resulting in more than 350,000 deaths every year (Siegel et al 2016; Sanderson and Ironside 2002). The anatomic location of the tumor usually impedes or inhibits proper patient nutrition; problems with proper ingestion are noted in even up to 50% of HNC patients In such individuals, undernutrition is frequently present at the time of diagnosis and it can be the first observable symptom of the disease. Patients with CC genotype had the highest risk of early death incidence; such individuals should be qualified for parenteral nutrition and supportive care at the time of diagnosis to improve further therapy outcomes. This is the first study demonstrating the relationship between TNF-α −1031T/C polymorphism and plasma level of TNF-α. This is the first paper investigating the role of TNF-α −1031T/C in cancer cachexia
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