The Role of IL-9 Polymorphisms and Serum IL-9 Levels in Carcinogenesis and Survival Rate for Laryngeal Squamous Cell Carcinoma

Abstract

Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients’ five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients’ survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.

Structural basis for the mechanism and antagonism of receptor signaling mediated by Interleukin-9 (IL-9)

“…The single nucleotide polymorphism (SNP) rs2069885 resulting in a T117M point mutation in hIL-9 has been linked to asthma exacerbation, laryngeal squamous cell carcinoma (LSCC) and gender-specific effects on lung function, cystic fibrosis, and RSV infections in infants ( 36 – 40 ). This is the most prevalent missense SNP in hIL-9, with an allele frequency of 0.11 according to the genome aggregation database.…”

Th2 Cytokines (Interleukin-5 and -9) Polymorphism Affects the Response to Anti-TNF Treatment in Polish Patients with Ankylosing Spondylitis

“…The rs2069885 polymorphism was also examined in an extended haplotype analysis of the IL9 gene in patients with laryngeal squamous cell carcinoma (LSCC). The haplotype containing the IL9 rs2069885 G variant was associated with a lower probability of LSCC development [ 47 ]. In addition, IL9 haplotype analysis also revealed an association of the rs2069885 polymorphism with a predisposition to age-related macular degeneration (AMD) [ 48 ].…”

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review

“…The BID5+ variant of TNFα TNFBID5 polymorphism was significantly associated with poor DFS [ 20 ]. The IL-9 rs1859430 polymorphism was significantly associated with OS so that the AA genotype was associated with poor OS compared to AG + GG genotypes [ 73 ]. Results on the association between IL-10 polymorphisms and HNSCC prognosis were contradictory; in one study, the CC genotype of IL-10 rs1800871 polymorphism (compared to CT + TT genotypes) and the CC genotype of IL-10 rs1800872 polymorphism (compared to CA + AA genotypes) were associated with a significantly better survival in HPV16 + OPSCC patients [ 41 ].…”