Association of IL‐1 polymorphisms and IL‐1 serum levels with susceptibility to nasopharyngeal carcinoma

Abstract

Previous studies demonstrated that the polymorphism of interleukin-1 (IL-1) produce alterations of the protein expression and may contribute to oncogenetic processes. The aim of this study was to investigate the relationship between IL-1A gene polymorphisms and NPC susceptibility and the influence of on IL-1α serum levels in cases versus controls. To test whether the genetic variants of IL-1A gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the -889C/T and rs3783553 polymorphisms between 248 patients with NPC and 296 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Serum IL-1α levels were measured by enzyme-linked immunosorbent assay. The rs3783553 (TTCA insertion or deletion) polymorphism of the IL-1A gene was significantly associated with the susceptibility to NPC. The variant homozygote genotype +/+ was associated with a significantly reduced risk of NPC as compared with the wild homozygote -/- genotype, and the serum IL-1α levels were significantly lower in individuals with homozygous +/+ genotypes. No association was found between the -889C/T polymorphisms and risk of NPC, and no statistically significant differences were found between rs3783553 polymorphism and clinical pathology indices. The IL-1A rs3783553 polymorphism might contribute to a risk of developing NPC by affecting the serum IL-1α secretion in the Chinese population.

A functional insertion/deletion polymorphism in the IL1A gene is associated with decreased risk of breast cancer

“…Recently, a novel functional polymorphism (rs3783553 TTCA/-) resident in miR-122 has been discovered, and is reported to affect the transcription of IL1A by changing the binding strength of miR-122 and miR-378 (Gao et al, 2009). The polymorphism has subsequently been reported to be related to decreased risk of HCC (Gao et al, 2009), nasopharyngeal carcinoma (Yang et al, 2011), and gastric cancer (Zeng et al, 2014). In this study, we evaluated the potential relationship between the ILIA rs3783553 insertion/deletion polymorphism and the risk of BC, and found that the ILIA rs3783553 ins/ins (ttca/ttca) genotype and the ins (ttca) allele distributions between cases and controls were significantly different.…”

“…A polymerase chain reaction (PCR) assay was used to analyze the IL1A gene rs3783553 polymorphism. Details of the primer sequences and reaction conditions have been described previously (Gao et al, 2009;Yang et al, 2011;Zeng et al, 2014). To confirm the accuracy of the genotyping, randomly selected PCR products were sequenced, and the results were verified.…”

“…The TTCA insertion allele is associated with the elevated transcription of IL-1A in vitro and in vivo. Subsequent studies showed that the rs3783553 ins/ins (TTCA/TTCA) genotype decreases susceptibility to hepatocellular carcinoma (Gao et al, 2009), nasopharyngeal carcinoma (Yang et al, 2011), and gastric cancers (Zeng et al, 2014).…”

Lack of association between an insertion/deletion polymorphism in IL1A and risk of colorectal cancer

“…reported that the IL1A rs3783553 ins/ins homozygous genotype is associated with a significantly reduced risk of hepatocellular carcinoma. Similarly, decreased risks were found for nasopharyngeal carcinoma (Yang et al, 2011), gastric cancer (Zeng et al, 2014), cervical carcinoma , and epithelial ovarian cancer (Zhang et al, 2014b). Furthermore, patients of this genotype demonstrated a reduced risk of developing stages T3 and T4 of papillary thyroid carcinoma (Gao et al, 2014) and poor cervical carcinoma tumor differentiation .…”

“…Further analysis revealed that this insertion may disrupt binding of miR-122/miR-378 to IL1A, thereby increasing expression of interleukin-1 alpha (IL-1a; ). Subsequently, several groups have investigated the relationship between this polymorphism and hepatocellular carcinoma (Du et al, 2014;Wang et al, 2014), nasopharyngeal carcinoma (Yang et al, 2011), gastric cancer (Zeng et al, 2014), papillary thyroid carcinoma (Gao et al, 2014), cervical carcinoma (Pu et al, 2014b), and epithelial ovarian cancer (Zhang et al, 2014). However, no study to date has assessed its association with CRC risk.…”