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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

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....

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Autores principales: Pooja, Singh, Francis, Amirtharaj, Rajender, Singh, Tamang, Rakesh, Rajkumar, Raja, Saini, Karan Singh, Megu, Kaling, Goel, Madhu Mati, Surekha, Daminani, Rao, Digumarthi Raghunatha, Rao, Lakshmi, Ramachandra, Lingadakai, Kumar, Sandeep, Kumar, Surender, Vishnupriya, Satti, Satyamoorthy, Kapaettu, Negi, Mahendra Pal Singh, Thangaraj, Kumarasamy, Konwar, Rituraj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798290/
https://www.ncbi.nlm.nih.gov/pubmed/24146803
http://dx.doi.org/10.1371/journal.pone.0075979
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author Pooja, Singh
Francis, Amirtharaj
Rajender, Singh
Tamang, Rakesh
Rajkumar, Raja
Saini, Karan Singh
Megu, Kaling
Goel, Madhu Mati
Surekha, Daminani
Rao, Digumarthi Raghunatha
Rao, Lakshmi
Ramachandra, Lingadakai
Kumar, Sandeep
Kumar, Surender
Vishnupriya, Satti
Satyamoorthy, Kapaettu
Negi, Mahendra Pal Singh
Thangaraj, Kumarasamy
Konwar, Rituraj
author_facet Pooja, Singh
Francis, Amirtharaj
Rajender, Singh
Tamang, Rakesh
Rajkumar, Raja
Saini, Karan Singh
Megu, Kaling
Goel, Madhu Mati
Surekha, Daminani
Rao, Digumarthi Raghunatha
Rao, Lakshmi
Ramachandra, Lingadakai
Kumar, Sandeep
Kumar, Surender
Vishnupriya, Satti
Satyamoorthy, Kapaettu
Negi, Mahendra Pal Singh
Thangaraj, Kumarasamy
Konwar, Rituraj
author_sort Pooja, Singh
collection PubMed
description 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<0.001). CONCLUSION: 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.
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spelling pubmed-37982902013-10-21 Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study Pooja, Singh Francis, Amirtharaj Rajender, Singh Tamang, Rakesh Rajkumar, Raja Saini, Karan Singh Megu, Kaling Goel, Madhu Mati Surekha, Daminani Rao, Digumarthi Raghunatha Rao, Lakshmi Ramachandra, Lingadakai Kumar, Sandeep Kumar, Surender Vishnupriya, Satti Satyamoorthy, Kapaettu Negi, Mahendra Pal Singh Thangaraj, Kumarasamy Konwar, Rituraj PLoS One Research Article 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<0.001). CONCLUSION: 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. Public Library of Science 2013-10-17 /pmc/articles/PMC3798290/ /pubmed/24146803 http://dx.doi.org/10.1371/journal.pone.0075979 Text en © 2013 Pooja et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pooja, Singh
Francis, Amirtharaj
Rajender, Singh
Tamang, Rakesh
Rajkumar, Raja
Saini, Karan Singh
Megu, Kaling
Goel, Madhu Mati
Surekha, Daminani
Rao, Digumarthi Raghunatha
Rao, Lakshmi
Ramachandra, Lingadakai
Kumar, Sandeep
Kumar, Surender
Vishnupriya, Satti
Satyamoorthy, Kapaettu
Negi, Mahendra Pal Singh
Thangaraj, Kumarasamy
Konwar, Rituraj
Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title_full Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title_fullStr Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title_full_unstemmed Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title_short Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study
title_sort strong impact of tgf-β1 gene polymorphisms on breast cancer risk in indian women: a case-control and population-based study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798290/
https://www.ncbi.nlm.nih.gov/pubmed/24146803
http://dx.doi.org/10.1371/journal.pone.0075979
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