Correlation of serum IL-18 level and IL-18 gene promoter polymorphisms to the risk of cervical cancer

Abstract

OBJECTIVE: To investigate the correlations of serum interleukin-18 (IL-18) level and IL-18 gene promoter polymorphisms to the development of cervical cancer (CC). METHODS: Five single nucleotide polymorphisms (SNPs) of the IL-18 gene promoter region at position rs5744224, rs1946519, rs1946518, rs5744225 and rs5744226 were detected by means of sequences analysis in 50 CC patients and 50 normal subjects that matched for age and residence, and their serum IL-18 level was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Two linkage SNP sites (rs1946519 and rs1946518) in the up-stream of IL-18 gene were identified to present 3 genotypes, namely TT-AA, GG-CC, and TG-AC. A significant difference in the frequency of the 3 genotypes was observed between the CC patients and the normal controls (chi 2=17.497, P=0.000). The frequency of T (A)/G (C) alleles was 42% (42/100) in normal controls and 73% (73/100) in patients, showing significant diference (chi 2=19.662, P=0.000). Serum IL-18 concentrations of the CC patients was significantly lower than that of the normal controls (95.470-/+18.827 vs 116.756-/+16.262 pg/ml, F=14.445, P=0.000). In the cancer patients, serum IL-18 was 90.668-/+20.363 pg/ml for TT-AA genotype, 119.641-/+15.338 pg/ml for GG-CC genotype, and 112.793-/+13.326 pg/ml for TG-AC genotype, showing significant differences (F=11.307, P=0.000). A significant interaction effect was suggested between IL-18 genotype and CC (F=4.223, P=0.018). CONCLUSION: IL-18 gene polymorphisms and serum IL-18 level are related to the development of CC, and two SNPs, rs1946518 and rs1946519, can be important genetic factors for the susceptibility of cervical neoplasms.