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Association Study of Transforming Growth Factor Beta 1 + 29 T/C exon 1 Polymorphism in Breast Cancer Patients from North Indian Population

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Abstract

Background: TGFB1 cytokine is involved in normal mammary epithelial development as well as in breast tumorigenesis. It has role in both breast tumor suppression and progression. TGFB1 gene has several single nucleotide polymorphisms (SNPs) many of which modulate the activity of TGFB1. Our aim in this study was to analyze TGFB1 + 29 polymorphism in breast cancer individuals from North Indian population. Methods: TGFB1 + 29 T/C polymorphism was analyzed using Sanger sequencing in 285 breast cancer patients and age matched 363 healthy controls from North Indian population. Next, transcript expression of 13 apoptotic genes, TRAIL, DR4, DR5, DcR1, DcR2, Bcl2, cytochrome c, Casp8L, Casp8, FlipS, FlipL, Casp3s and Casp3 were carried out in 77 breast tumor tissues obtained from 77 individuals. Results: TGFB1 + 29 CC genotype provided protection against the development of breast cancer (P = 0.012). This was mainly attributable to higher age group (> 45 years) women (P = 0.016). Individuals having CC protector genotype showed significantly higher expression of TGFB1 transcript compared to the TT and TC risk genotypes (P = 0.044). Furthermore, we observed that TGFB1 + 29 CC genotype showed increased TRAIL mediated apoptosis via the extrinsic pathway in breast tumor patients with age greater than 45 years (P = 0.027). Conclusion: TGFB1 + 29 homozygous mutant CC genotype is related to protection against breast cancer in North Indian women population greater than 45 years of age.

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Data Availability

The data that supports the findings of this study are available from the corresponding author, RP, upon reasonable request.

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Acknowledgements

We thank Prof. R.N.K Bamezai (Jawaharlal Nehru University, New Delhi, India) for providing research facilities for carrying out the research work, critically reading and commenting on the manuscript which is based on the thesis work of RP carried out at Jawaharlal Nehru University, New Delhi, India (http://hdl.handle.net/10603/14169). We acknowledge Dr. Pawan Gupta of Dharamshila Cancer Hospital and Research Centre, Delhi, Dr. Neeraj Prakash from Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India and Dr. Gaurav Agarwal from Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India for providing the authors with the samples to carry out the research work in breast cancer biology. The authors further thank the patient and control subjects for their participation.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India

    Ranjana Pal

  2. Department of Life Sciences, Jawaharlal Nehru University, New Delhi, India

    Ranjana Pal & Siddhartha Dutta

  3. Department of Biotechnology, University of Engineering and Management, Kolkata, West Bengal, India

    Siddhartha Dutta

  4. Department of Microbiology and Biotechnology, Sister Nivedita University, Kolkata, West Bengal, India

    Siddhartha Dutta

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Correspondence to Ranjana Pal.

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Supplementary Material 1

Supplementary Fig. 1

Categorization of gene expression belonging to extrinsic and intrinsic apoptotic pathways (TRAIL, DR4, DR5, Casp8, Casp3, TRAIL, DcR1, DcR2, Casp8L, FlipL, FlipS, Casp3s, Cytochrome c, Casp3, Bcl2, Casp3s) with respect to age (≤ 45 and > 45 years) which are further categorized with respect to TGFB1 + 29 genotype. * indicates p value less than equal to 0.05. # indicates p value less than equal to 0.09 but more than 0.05. Error bars represents standard error.

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Pal, R., Dutta, S. Association Study of Transforming Growth Factor Beta 1 + 29 T/C exon 1 Polymorphism in Breast Cancer Patients from North Indian Population. Appl Biochem Biotechnol 195, 3671–3680 (2023). https://doi.org/10.1007/s12010-023-04438-5

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