Strong impact of TGF-b1 gene polymorphisms on breast cancer risk in Indian women: A case-control and population-based study

Rao, Lakshmi and Ramachandra, L and Satyamoorthy, K (2013) Strong impact of TGF-b1 gene polymorphisms on breast cancer risk in Indian women: A case-control and population-based study. PLoS ONE, 8 (10). pp. 1-9.

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Introduction: TGF-b1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGFb1 signaling in breast cancer progression is well documented. Some TGF-b1 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-b1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-b1 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-b1 was significantly elevated in patients in comparison to controls (p,0.001). Conclusion: c.29C.T and c.74G.C polymorphisms in the TGF-b1 gene significantly affect breast cancer risk, which correlates with elevated TGF-b1 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.

Item Type: Article
Subjects: Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Pathology
Medicine > KMC Manipal > Surgery
Depositing User: KMC Manipal
Date Deposited: 24 Dec 2013 09:18
Last Modified: 23 Nov 2016 09:20

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