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


CONCLUSIONS
TNF-LTA locus could serve as an important biomarker for breast cancer predisposition in Indian population.
Kohaar
Indu
I
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
Tiwari
Pratibha
P
Kumar
Rakesh
R
Nasare
Vilas
V
Thakur
Nisha
N
Das
Bhudev C
BC
Bharadwaj
Mausumi
M
D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D004273:DNA, Neoplasm; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha