sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

Abstract

Programmed cell death called apoptosis, plays an important role in the development and maintenance of tissue homeostasis and abnormalities in apoptotic function have been known as important events in the pathogenesis of many cancer types, such as colorectal cancer. It has been shown that both the membrane-bound TRAIL and sTRAIL can induce apoptosis in several tumor types by activating death receptors. Our study was to investigate the existence of TRAIL 1595 C/T SNP in colorectal cancer patients and possible effects of this substitution on serum levels of sTRAIL. In the present study, TRAIL 1595 C/T polymorphism was genotyped in 76 patients with colorectal cancer and 98 healthy subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There were no significant differences in the distribution of TRAIL 1595 C/T genotypes and frequencies of the alleles between colorectal cancer patients and controls. The increased frequency of TRAIL 1595 homozygotes genotypes in patients who had advanced tumour stage was statistically significant (p = 0.0082). Serum sTRAIL levels in the colorectal patients with CT genotype were lower than those of patients with early tumor stage (p = 0.028). The decreased sTRAIL levels were observed in the patients with distant metastasis and CT genotype (p = 0.023).Our findings have suggested that TRAIL 1595 C/T genotypes and sTRAIL levels might be associated with the progression of colorectal cancer in Turkish population.

Effect of trail C1595T variant and gene expression on the pathogenesis of non-small cell lung cancer

“…In our study, although not statistically significant, the C1595T CT + TT genotype and T allele frequency were lower in stage III and IV NSCLC patients than that of found in stage I and II patients (frequencies of CT+ TT genotype: 29.4% and 39.2%, T allele: 26.5% and 39.2%, respectively), and our results are inconsistent with the results of Luo et al When we approach this issue as general carcinogenesis, Wang et al found that the frequency of TRAIL C1595T variant T carriage in patients with poorly differentiated gastric adenocarcinoma was significantly lower [20]. Yaylım et al found that TRAIL C1595T CC and homozygous CC + TT genotypes frequency were significantly higher in patients with advanced stage tumors of colorectal cancer than in patients with early stage tumors [12]. Yildiz et al detected TRAIL C1595T CT genotype at a significantly lower frequency in patients with advanced stage tumor than those with early stage tumor in breast cancer [13].…”

“…Timirci-Kahraman et al found that the frequency of TRAIL 1595 TT genotype was lower in bladder cancer patients than in healthy controls, and the frequency of CT genotype was significantly higher [21]. Yaylım et al in patients with colorectal cancer [12] and Yıldız et al in patients with breast cancer [13] did not find any significant difference in TRAIL C1595T genotype distribution. In our study, we have considered the frequency of this genotype and alleles in Turkish cases.…”

“…TRAIL-R1 and TRAIL-R2 contain cytoplasmic death domain and induce apoptosis after ligand binding. The death domain of TRAIL-R3, TRAIL-R4, and OPG is either truncated or lack and cannot induce apoptosis [8,12,13]. TRAIL has been shown to be expressed at the protein and mRNA level in different tissue such as liver, lung, placenta, kidney, spleen, heart, ovary, small and large intestine, and also in several cells, including immune cells [14–16].…”

“…The TRAIL gene located on chromosome 3q26 is approximately 20 kb in length [17,18], and this gene which encodes an mRNA of 1.77 kb is composed of 5 exons and 4 introns [12,13]. Despite the fact that polymorphisms of TRAIL have been reported in various cancers such as lung cancer [6], colon cancer [12], breast cancer [13,19], gastric cancer [20], bladder cancer [21], prostate cancer [22], and renal cancer [23], in some diseases such as type 2 diabetes mellitus [24], intervertebral disc disorder [25], multiple sclerosis [26], ulcerative colitis [27], and fatty liver disease [28].…”

“…Despite the fact that polymorphisms of TRAIL have been reported in various cancers such as lung cancer [6], colon cancer [12], breast cancer [13,19], gastric cancer [20], bladder cancer [21], prostate cancer [22], and renal cancer [23], in some diseases such as type 2 diabetes mellitus [24], intervertebral disc disorder [25], multiple sclerosis [26], ulcerative colitis [27], and fatty liver disease [28]. However, the role of TRAIL polymorphism in lung cancer is yet to be elucidated [29].…”