Colorectal cancer severity and survival in correlation with tumour necrosis factor-alpha

Abstract

Colorectal cancer (CRC) development is strongly associated with innate immune mechanisms and intestinal inflammation. The aim of the study was to investigate the pre-operative serum levels of TNF-α and its correlation with cancer progression and survival in CRC patients taking into account the genotype of –308G/A promoter polymorphism in TNF-α gene (rs1800629). TNF-α –308G/A genotypes of 119 CRC cases and 177 no CRC controls were determined by restriction fragment length polymorphism assay (RFLP-PCR). TNF-α serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Although no significant differences in allele and genotype frequencies between CRC and controls were observed, it should be noted that the minor allele-A and its homozygous genotype were overrepresented among CRC. In addition, allele-A was more frequent in early CRC patients compared to advanced cases. TNF-α serum level was significantly higher in CRC patients than in controls (36.1 ± 8.4 pg/mL vs. 18.66 ± 11 pg/mL; p = 0.0000001). In the subgroup analysis by tumour–node–metastasis stages, the highest TNF-α level was found in stage IV (42.7 ± 12.5 pg/mL) and was significantly elevated compared to earlier stages of CRC and controls. The survival rate of CRC patients with low TNF-α serum level, estimated as median survival, was significantly higher than that of patients with high levels of TNF-α (38.4 vs. 7.761 months; log rank test p = 0.00015) In conclusion, we can affirm that TNF-α affects tumour development along with disease progression which has an impact on the survival of CRC.

Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients

“…Other studies have described similar results (Shimazaki et al, 2013;Stanilov et al, 2014). However, there was no association between TNF-α levels and -308G>A and -238G>A polymorphism haplotypes in Mexican CRC patients and controls.…”

“…The rs361525 minor allele is only present in the heterozygous genotype, and has previously been reported to be present at a frequency of 0.1-0.2%, based on different population data (Mohamed et al, 2010;Vázquez-Huerta et al, 2014). Although these polymorphisms have been connected to various diseases, including CRC (Fan et al, 2011;Shen et al, 2011;Cereda et al, 2012;Chu et al, 2012;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014;Vázquez-Huerta et al, 2014), study results have been inconsistent. The aim of this investigation was to measure TNF-α concentration in the plasma of Mexican CRC patients and determine its relationship with the -308G>A and -238G>A polymorphisms and haplotypes of the TNF-α gene.…”

“…In vitro and in vivo studies have shown that high levels of TNF-α are associated with poor prognoses in cancer patients due to its tumorigenic effects (Champ et al, 2012;Gómez Flores-Ramos et al, 2013). Several studies have demonstrated a significant association between cytokine levels and increased CRC risk (Fan et al, 2011) or severity (Stanilov et al, 2014). However, others have failed to establish a link between TNF-α and susceptibility to this disease (Landi et al, 2006;Crucitti et al, 2015).…”

“…The -308 (rs1800629) and -238 (rs361525) polymorphisms in the promoter region of the TNF-α gene have been reported to correlate with increased TNF-α production (Cereda et al, 2012). Studies have also associated these polymorphisms with complex diseases, including breast cancer and CRC (Fan et al, 2011;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014). According to National Center for Biotechnology Information 2012 population data, the rs1800629 minor allele (A) frequency is 5-10, 0.8-14, 0-2, and 0-8% among European, African, Asian, and Mexican populations, respectively (Parra-Rojas et al, 2006;Gómez Flores-Ramos et al, 2013).…”

Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis factor alpha levels in patients with gastric cancer

“…The patients with stage IV disease had the highest TNF-α level, and this elevation was significant compared to earlier stages of disease and controls. Furthermore, the median survival of patients with low serum TNF-α level was significantly improved compared to patients with high level of TNF-α (p=00015) [58].…”