Tumor Necrosis Factor Alpha and Beta and Interferon Gamma Gene Polymorphisms in Turkish Breast Cancer Patients

Abstract

Cytokine genes are important for researching cancer predisposition to cancers that elicit anti-tumor immune response. In this study, we investigated the association between breast cancer and tumor necrosis factor alpha (TNF-alpha) -308 (G>A), TNF-beta +252 (A>G), and interferon gamma (IFN-gamma) +874 (T>A) gene polymorphisms in a Turkish population. This study involved 204 female breast cancer patients and 204 healthy female controls. Genomic DNA was extracted from EDTA-preserved peripheral venous blood of patients and controls by a salting-out method and analyzed by polymerase chain reaction, allele-specific oligonucleotide polymerase chain reaction, and restriction fragment length polymorphism. TNF-alpha -308 genotype was found to have no effect on breast cancer susceptibility. However, there were statistically significant differences between the genotype frequencies of patients and controls for TNF-beta polymorphism (p = 0.016) and the allele and genotype frequencies for the IFN-gamma polymorphism (p = 0.0312 and p = 0.001, respectively). In the composite genotype analysis, the TNF-alpha/beta GAAG composite genotype (p = 0.0424), the TNF-alpha/IFN-gamma GGTT and GATT composite genotypes (p = 0.0296 and p = 0.0129, respectively), the TNF-beta/IFN-gamma AGTT composite genotype (p = 0.0003), and the TNF alpha/beta/IFN-gamma GGAGTT and GAAGTT composite genotypes (p = 0.0437 and p = 0.0038, respectively) were estimated to have a protective effect against breast cancer. However, the TNF-alpha/IFN-gamma GGTA composite genotype is a risk factor for breast cancer (p = 0.0156). In conclusion, TNF-beta +252GG genotype was found more frequent in Turkish breast cancer patients than controls and IFN-gamma TA+AA genotypes were estimated to increase breast cancer risk significantly in Turkish population.