title: Strong impact of TGF-β1 gene polymorphisms on breast cancer risk in Indian women: a case-control and population-based study.
abstract: BACKGROUND
  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<0.001).
  
  
  CONCLUSIONS
  c.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.
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India ; Department of Pathology, King George's Medical University, Lucknow, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Pooja
authors.forename: Amirtharaj
authors.initials: A
authors.lastname: Francis
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tamang
authors.forename: Raja
authors.initials: R
authors.lastname: Rajkumar
authors.forename: Karan Singh
authors.initials: KS
authors.lastname: Saini
authors.forename: Kaling
authors.initials: K
authors.lastname: Megu
authors.forename: Madhu Mati
authors.initials: MM
authors.lastname: Goel
authors.forename: Daminani
authors.initials: D
authors.lastname: Surekha
authors.forename: Digumarthi Raghunatha
authors.initials: DR
authors.lastname: Rao
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rao
authors.forename: Lingadakai
authors.initials: L
authors.lastname: Ramachandra
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Surender
authors.initials: S
authors.lastname: Kumar
authors.forename: Satti
authors.initials: S
authors.lastname: Vishnupriya
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
authors.forename: Mahendra Pal Singh
authors.initials: MP
authors.lastname: Negi
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D002277:Carcinoma / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D044465:White People
chemical_list: D053773:Transforming Growth Factor beta1