Zidi Sabrina, Stayoussef Mouna, Alsaleh Bano L, Gazouani Ezzedine, Mezlini Amel, Ebrahim Bashayer H, Yacoubi-Loueslati Besma, Almawi Wassim Y
Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, El Manar University, 1092, Tunis, Tunisia.
Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
Pathol Oncol Res. 2017 Apr;23(2):385-392. doi: 10.1007/s12253-016-0127-9. Epub 2016 Oct 8.
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.
我们研究了六种常见和新型白细胞介素-6（IL-6）基因多态性与突尼斯人宫颈癌（CC）风险之间的关联。研究对象包括112例CC病例和164名对照女性。通过实时PCR对IL-6 rs2069845、rs2069840、rs1474348、rs1800795、rs1800797、rs2069827变体进行基因分型，并确定聚类。CC患者和对照女性之间，所检测的IL-6单核苷酸多态性（SNP）的等位基因和基因型分布具有可比性。根据国际妇产科联盟（FIGO）分期进行分层分析显示，rs1800795纯合主要等位基因基因型（P = 0.033；比值比（OR）= 0.49（0.25 - 0.95））和主要等位基因（P = 0.037；OR = 0.57（0.33 - 0.97））对CC具有保护作用。此外，rs1474348主要等位基因的携带也对CC具有保护作用（P = 0.014；OR = 0.53（0.32 - 0.88）），而在FIGO早期阶段的CC患者中观察到rs1474348次要等位基因频率较高（P = 0.044；OR = 0.39（0.15 - 1.00）），因此表明rs1474348与CC的血管生成演变和进展有关。Haploview分析表明，rs2069845、rs2069840、rs1474348和rs1800795之间存在高度连锁不平衡（LD），六基因座单倍型分析确定GACCCA单倍型与CC增加呈正相关，而GAGGGG单倍型与CC呈负相关，因此表明该单倍型对CC具有保护作用。此外，CC发病率与使用激素避孕（P = 0.047；OR = 1.97（0.94 - 4.13））和吸烟（P < 0.001；OR = 7.12（2.97 - 17.04））之间存在显著关联。IL-6变体rs1800795和rs1474348、单倍型GACCCA和GAGGGG，以及激素避孕的使用和吸烟，是突尼斯女性CC易感性和演变的主要危险因素。
