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Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

Author

Listed:
  • Singh Pooja
  • Amirtharaj Francis
  • Singh Rajender
  • Rakesh Tamang
  • Raja Rajkumar
  • Karan Singh Saini
  • Kaling Megu
  • Madhu Mati Goel
  • Daminani Surekha
  • Digumarthi Raghunatha Rao
  • Lakshmi Rao
  • Lingadakai Ramachandra
  • Sandeep Kumar
  • Surender Kumar
  • Satti Vishnupriya
  • Kapaettu Satyamoorthy
  • Mahendra Pal Singh Negi
  • Kumarasamy Thangaraj
  • Rituraj Konwar

Abstract

Introduction: TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. Methods: We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA. Results: c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.

Suggested Citation

  • Singh Pooja & Amirtharaj Francis & Singh Rajender & Rakesh Tamang & Raja Rajkumar & Karan Singh Saini & Kaling Megu & Madhu Mati Goel & Daminani Surekha & Digumarthi Raghunatha Rao & Lakshmi Rao & Lin, 2013. "Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    • Handle: RePEc:plo:pone00:0075979
    DOI: 10.1371/journal.pone.0075979
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    1. David Reich & Kumarasamy Thangaraj & Nick Patterson & Alkes L. Price & Lalji Singh, 2009. "Reconstructing Indian population history," Nature, Nature, vol. 461(7263), pages 489-494, September.
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