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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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<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.

Original languageEnglish
Article numbere75979
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - 17-10-2013

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Polymorphism
breast neoplasms
Genes
genetic polymorphism
Breast Neoplasms
Population
genes
menopause
nationalities and ethnic groups
loci
Nepal
Molecular Epidemiology
Substitution reactions
Population Genetics
Genetic Association Studies
Association reactions
DNA Sequence Analysis
Carcinogenesis
Breast
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pooja, S., Francis, A., Rajender, S., Tamang, R., Rajkumar, R., Saini, K. S., ... Konwar, R. (2013). Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study. PLoS One, 8(10), [e75979]. https://doi.org/10.1371/journal.pone.0075979
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. In: PLoS One. 2013 ; Vol. 8, No. 10.
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title = "Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study",
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<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.",
author = "Singh Pooja and Amirtharaj Francis and Singh Rajender and Rakesh Tamang and Raja Rajkumar and Saini, {Karan Singh} and Kaling Megu and Goel, {Madhu Mati} and Daminani Surekha and Rao, {Digumarthi Raghunatha} and Lakshmi Rao and Lingadakai Ramachandra and Sandeep Kumar and Surender Kumar and Satti Vishnupriya and Kapaettu Satyamoorthy and Negi, {Mahendra Pal Singh} and Kumarasamy Thangaraj and Rituraj Konwar",
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Pooja, S, Francis, A, Rajender, S, Tamang, R, Rajkumar, R, Saini, KS, Megu, K, Goel, MM, Surekha, D, Rao, DR, Rao, L, Ramachandra, L, Kumar, S, Kumar, S, Vishnupriya, S, Satyamoorthy, K, Negi, MPS, Thangaraj, K & Konwar, R 2013, 'Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study', PLoS One, vol. 8, no. 10, e75979. https://doi.org/10.1371/journal.pone.0075979

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.

In: PLoS One, Vol. 8, No. 10, e75979, 17.10.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women

T2 - A Case-Control and Population-Based Study

AU - Pooja, Singh

AU - Francis, Amirtharaj

AU - Rajender, Singh

AU - Tamang, Rakesh

AU - Rajkumar, Raja

AU - Saini, Karan Singh

AU - Megu, Kaling

AU - Goel, Madhu Mati

AU - Surekha, Daminani

AU - Rao, Digumarthi Raghunatha

AU - Rao, Lakshmi

AU - Ramachandra, Lingadakai

AU - Kumar, Sandeep

AU - Kumar, Surender

AU - Vishnupriya, Satti

AU - Satyamoorthy, Kapaettu

AU - Negi, Mahendra Pal Singh

AU - Thangaraj, Kumarasamy

AU - Konwar, Rituraj

PY - 2013/10/17

Y1 - 2013/10/17

N2 - 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.

AB - 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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