PLoS ONE (Jan 2013)

Strong impact of TGF-β1 gene polymorphisms on breast cancer risk in Indian women: a case-control and population-based study.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0075979
Journal volume & issue
Vol. 8, no. 10
p. e75979

Abstract

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IntroductionTGF-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.MethodsWe 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.Resultsc.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 (pConclusionc.29C>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.