Thriveni Karuvaje, Raju Anisha, Ramaswamy Girija, Krishnamurthy S
Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India.
Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India.
Indian J Cancer. 2018 Apr-Jun;55(2):179-183. doi: 10.4103/ijc.IJC_591_17.
Inflammation plays a lead role in the tumor microenvironment and promotes metastasis. Single-nucleotide polymorphism (SNP) in the tumor necrosis factor (TNF) gene locus may alter the expression of genes and proteins. The objective of the study is to find the distribution of genetic polymorphism in the sites of TNF-α -308G>A and TNF- β +252A>G in breast cancer and evaluate polymorphism effects on plasma levels.
The study group consisted of 109 invasive ductal primary breast cancer patients and 75 age-matched healthy female controls. Plasma cytokine concentrations were measured by the MILLIPLEX MAP Human Cytokine/Chemokine Panel magnetic bead kits. The genotyping procedure for SNP included allele-specific polymerase chain reaction for TNFα and restriction fragment length polymorphism for TNFβ.
Odds ratio with 95% confidence interval showed that these polymorphisms were not a causative risk factor, and both polymorphisms were consistent with Hardy-Weinberg equilibrium. Plasma TNFα and TNFβ median concentrations were significantly higher in cases when compared to controls (P < 0.01). When plasma TNFα levels were grouped under polymorphic subtypes, patients with mutant TNF- α -308A allele showed significantly higher values (P < 0.001). In addition, plasma TNFα values were significantly elevated in mutant TNF-β +252G allele (P < 0.01).
This study demonstrated that there is no significant association between SNPs and breast cancer susceptibility in South Indian population. However, plasma TNFα level is significantly elevated with mutant-recessive TNF-α -308 A and TNF-β +252 G alleles of patients.
炎症在肿瘤微环境中起主导作用并促进转移。肿瘤坏死因子(TNF)基因位点的单核苷酸多态性(SNP)可能会改变基因和蛋白质的表达。本研究的目的是发现乳腺癌中TNF-α -308G>A和TNF-β +252A>G位点的基因多态性分布,并评估多态性对血浆水平的影响。
研究组由109例浸润性导管原发性乳腺癌患者和75例年龄匹配的健康女性对照组成。采用MILLIPLEX MAP人细胞因子/趋化因子磁珠试剂盒检测血浆细胞因子浓度。SNP的基因分型程序包括TNFα的等位基因特异性聚合酶链反应和TNFβ的限制性片段长度多态性分析。
95%置信区间的优势比表明这些多态性不是致病危险因素,且两种多态性均符合Hardy-Weinberg平衡。与对照组相比,病例组血浆TNFα和TNFβ的中位数浓度显著更高(P < 0.01)。当血浆TNFα水平按多态性亚型分组时,携带突变型TNF-α -308A等位基因的患者的值显著更高(P < 0.