Association of single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer risk in Indian population

Abstract

Cytokine milieu of tumor microenvironment affects tumorigenesis in breast cancer. The aim of the present study was to investigate the potential association of functional single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer. The study included 127 individuals comprising 40 breast cancer cases (35 sporadic & 5 familial) and 87 individuals of high risk group (with family history of breast cancer) along with 150 healthy controls. PCR-RFLP was employed to analyze TNFA promoter polymorphisms at -238 G/A, -308 G/A, -857 C/T, -863 C/A and -1031 T/C along with +252 A/G SNP in LTA. The results were further confirmed by direct sequencing. Significant association was established for TNFA -308 G/A and LTA +252 A/G polymorphisms with breast cancer versus controls (P < 0.0001; OR, 9.53; 95% CI, 4.11-22.13; P (c) < 0.001) and high risk group versus controls (P < 0.0001; OR, 8.27; 95% CI, 4.28-16.0; P (c) < 0.001) respectively. GGACCT haplotype was found to be positively associated with breast cancer (P < 0.0001; OR, 12.17; 95% CI = 5.12-28.92; P (c) < 0.001) and high risk group (P, 0.03; OR, 2.95; 95% CI, 1.20-7.26; P (c), 0.005) in relation to controls. While GGGCCT haplotype was significantly related with high risk group in comparison to cancer (P, 0.0002; OR, 5.71; 95% CI, 2.18-14.99; P (c), 0.003) and controls (P, 0.0002; OR, 2.48; 95% CI, 1.55-3.96; P (c), 0.003). TNF-LTA locus could serve as an important biomarker for breast cancer predisposition in Indian population.