Department of Genetics, Osmania University, Hyderabad, Telangana State, India; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, India.
Department of Genetics, Osmania University, Hyderabad, Telangana State, India.
Cytokine. 2022 Dec;160:156024. doi: 10.1016/j.cyto.2022.156024. Epub 2022 Sep 28.
Cytokines are multifunctional glycoproteins that play a vital role in the tumor microenvironment and progression of breast cancer. Genetic polymorphisms may influence the immune responses restrained by pro- and anti-inflammatory cytokine expression in tumors. Hence, the present study evaluated the contribution of Interleukin (IL) 6 (rs1800797, rs1800796, and rs1800795) and IL18 (rs1946518, rs187238, and rs549908) genotypes and their haplotypes to the risk, progression of breast cancer in South Indian population. The polymorphisms of IL6 -597G > A, -572C > G & -174G > C, and IL18 -607C > A, -137G > C, 105A > T were genotyped through PCR-RFLP and As-PCR assays in the blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression, and Kaplan-Meier analyses for the obtained data. The frequency of AA genotype & A-allele of IL6 -597G > A, and CC genotype & C-allele of IL6 -174G > C polymorphism was higher in breast cancer patients and was found to be significantly associated with late (advanced) stage, metastasis, etc. Further, IL18 -607C > A, -137G > C, and 105A > T polymorphisms were found to be associated with lobular carcinoma subtype, PgR -ve, and HER2 +ve breast cancer patients. In survival analysis, we have observed that the C-allele of IL6 -174G > C polymorphism to be significantly associated with 5 years of overall survival in breast cancer subjects. All SNPs of the IL6 and IL18 genes showed perfect LD; the G-C-C, A-G-G, and A-C-C haplotype combinations of IL6 gene conferred 2.09, 2.25, and 4.72 folds risk for breast cancer respectively. Hence, our results suggest the importance of genotypic and haplotype analysis of IL6 and IL18 gene variants in the progression and risk prediction of breast cancer.
细胞因子是多功能糖蛋白，在肿瘤微环境和乳腺癌的进展中起着至关重要的作用。遗传多态性可能会影响肿瘤中促炎和抗炎细胞因子表达所抑制的免疫反应。因此，本研究评估了白细胞介素（IL）6（rs1800797、rs1800796 和 rs1800795）和 IL18（rs1946518、rs187238 和 rs549908）基因座的基因型及其单倍型在印度南部人群乳腺癌风险和进展中的作用。通过 PCR-RFLP 和 As-PCR 检测 600 例受试者血液 DNA 中的 IL6-597G>A、-572C>G 和-174G>C 以及 IL18-607C>A、-137G>C 和 105A>T 多态性。我们对获得的数据进行了单倍型、LD、单变量、多变量逻辑回归和 Kaplan-Meier 分析。IL6-597G>A 的 AA 基因型和 A 等位基因，以及 IL6-174G>C 多态性的 CC 基因型和 C 等位基因在乳腺癌患者中的频率更高，并且与晚期（进展期）、转移等显著相关。此外，IL18-607C>A、-137G>C 和 105A>T 多态性与小叶癌亚型、PgR-阴性和 HER2 阳性乳腺癌患者有关。在生存分析中，我们观察到 IL6-174G>C 多态性的 C 等位基因与乳腺癌患者 5 年总生存率显著相关。IL6 和 IL18 基因的所有 SNP 均显示出完美的 LD；IL6 基因的 G-C-C、A-G-G 和 A-C-C 单倍型组合分别赋予乳腺癌 2.09、2.25 和 4.72 倍的风险。因此，我们的结果表明，对 IL6 和 IL18 基因变异的基因型和单倍型分析在乳腺癌的进展和风险预测中具有重要意义。
