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

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.

Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk.

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46-17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01-0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.