Relationships between Common and Novel Interleukin-6 Gene Polymorphisms and Risk of Cervical Cancer: a Case-Control Study

Abstract

We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P=0.033; OR =0.49(0.25-0.95)) and major allele (P=0.037; OR=0.57 (0.33-0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P=0.014; OR=0.53(0.32-0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P=0.044; OR=0.39 (0.15-1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P=0.047; OR=1.97 (0.94-4.13)) and smoking (P<0.001; OR=7.12 (2.97-17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.