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

  • Epidemiology
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Abstract

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.

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Acknowledgements

The authors thank patients, their relatives and clinicians for their support and cooperation. We also acknowledge the help of Dr. L. Satyanarayan ICPO, for his statistical advice and Jitender Kumar IGIB, Delhi, for providing technical support. IK and RK are grateful to The Indian Council of Medical Research (ICMR) and Council of Scientific and Industrial Research (CSIR) for their Senior Research Fellowships. The study was supported in part by funds provided by CSIR 60(0075)/06/EMR-II, Govt. of India (PT) and core funds of ICPO (ICMR), Noida.

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  1. Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, 201301, India

    Indu Kohaar, Pratibha Tiwari, Vilas Nasare, Nisha Thakur & Mausumi Bharadwaj

  2. Division of Molecular Oncology, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India

    Rakesh Kumar & Bhudev C. Das

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  1. Indu Kohaar
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Correspondence to Mausumi Bharadwaj.

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Kohaar, I., Tiwari, P., Kumar, R. et al. Association of single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer risk in Indian population. Breast Cancer Res Treat 114, 347–355 (2009). https://doi.org/10.1007/s10549-008-0006-5

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