Genetic Polymorphism in TNF-α-308 G/A and TNF-β +252 A/G, as Prognostic Biomarker in Breast Cancer Patients among Indian Population

Abstract

Background: Cytokines are the key regulator molecules that modulate immune response. Tumor necrosis factor (TNF-α-308 G/A and TNF-β +252 A/G) are inflammatory cytokine that control the progression of several types of cancer. They play a vital role in both tumor progression and destruction based on their concentrations. The role of TNF-α-308 G/A and TNF-β +252 A/G gene polymorphism in the etiology of breast cancer (BC) is not clearly understood. Therefore, present study investigates the association of TNF-α-308 G/A and TNF-β +252 A/G and the clinical features with Breast cancer patients. Methods: In a case-control study, we have investigated 150 breast cancer patients and 300 age and ethnically matched healthy controls for duration of 3 years from North India. Promoter polymorphisms of tumor necrosis factor gene (TNF-α-308 G/A and TNF-β +252 A/G) were genotyped using allele specific oligonucleotide polymerase chain reaction ASO and restriction fragment length polymorphism (PCR-RFLP). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI) using SPSS. Results: Patients with different clinico-pathological variables and healthy controls were analyzed. Significant association was observed in A allele of TNF-α-308 G/A in breast cancer patients as compared to healthy controls (p<0.0001). However, no association was seen in TNF-β +252 A/G both at genotypic and allelic level. The GG genotype of TNF-β +252A/G is higher in grades III (p<0.01) patients. Conclusion: Our results suggest that TNF-α-308G/A polymorphism showed significant association with breast cancer patients.

Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories

“…Results of the study of Ahmad et al. ( 37 ) among an Indian population, suggest that TNF-α-308G/A polymorphism showed significant association with breast cancer patients ( 37 ). Our results show that the mutant TNF-α variant of 308 G/A was significantly associated with increased risk of cachexia in both the pancreatic and NSCL cancer patients.…”

Association between five types of Tumor Necrosis Factor-α gene polymorphism and hepatocellular carcinoma risk: a meta-analysis

“…A study by Skoog et al proposed that TNF-α − 863 C/A polymorphism affects the binding of nuclear protein(s) to the promoter region of the TNF-α gene, with accompanying changes in TNF-α expression, thus leading to variation in TNF-α levels [ 55 ]. The role of ethnicity may also play a role as well, carriers of the rare ‘A’ allele have a significantly lower TNF-α levels in Swedish and Indian population [ 55 , 56 ], while they have a significantly higher levels in Japanese population [ 52 , 53 ].…”

“…Of all other TNF-α SNPs, − 308 G/A is the most studied SNP. This SNP is also correlated with the risk of other cancer, such as breast cancer and gastric cancer [ 56 , 58 ]. This SNP seems to be variable within ethnicities, as in meta-analysis study conducted by Wei et al, SNP − 308 AA was associated with an increased risk of HCC in Asian ethnicities, but not for Caucasian [ 51 ].…”

A Quest for New Cancer Diagnosis, Prognosis and Prediction Biomarkers and Their Use in Biosensors Development

“…Recently were reported mutations of immune players as biomarkers, analyzed for specific human populations, Ahmad et al 104 reported the TNF-a308 G/A change and its significant association with breast cancer patients from north India and over the major histocompatibility complex class I-related chain A (MICA). Ouni et al 105 reported the MICA-129 Met/Val change as an inherited genetic biomarker contributing to an increased breast cancer risk in Tunisian women.…”