Association of Single Nucleotide Polymorphisms (SNPs) in TNF-LTA Locus with Breast Cancer Risk in Indian Population

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: TNF-LTA locus could serve as an important biomarker for breast cancer predisposition in Indian population.