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

Mohammad Margoob Ahmad,Farah Parveen,Naseem Akhter,Syed Akhtar Husain,Nootan Kumar Shukla,Jamshaid Ahmad Siddiqui

doi:10.31557/apjcp.2020.21.2.301

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.

Highlights

Breast cancer is one of the major cancers affecting the mortality of women worldwide (Jemal et al, 2008)
Our results suggest that Tumour Necrosis Factor (TNF)-α-308G/A polymorphism showed significant association with breast cancer patients
We provided evidence that patients with Tumour necrosis factor- α (TNF-α) -308A allele had an increased risk of tumor metastasis

Summary

Introduction

Breast cancer is one of the major cancers affecting the mortality of women worldwide (Jemal et al, 2008). TNF-α 308G/A is a G to A transition at nucleotide position 308 in the promoter region of the gene and TNF-β 252 A/G is a A to G transition at nucleotide position 252 in the promoter region of the gene It has been shown in previous studies that polymorphisms of TNF-α at positions 308 and 238 (i;e TNF2 and TNFA alleles) are associated with increased release of TNF-α (D’Alfonso et al.,1994; Kroeger et al.,1997). The role of TNF-α is important in cancer development common functional polymorphisms (rs1800629 and rs361525) have been examined extensively in many studies. Many studies have explained the association between cytokine polymorphism and development of different cancers including chronic lymphocytic leukemia, non-Hodgkin lymphoma and breast cancer (Howell et al, 2007). In present case-control study we have tried to correlate the role of TNF-α -308G /A and TNF-β +252 A/G in Breast Cancer susceptibility by ER, PR and Her status and the relationship between genotypes and clinicopathological characteristics of Breast Cancer

Materials and Methods

Results

A Allele

Discussion