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Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women

To determine the hypermethylation status of the promoter regions of tumour suppressor genes in breast tissues from healthy women and identify the determinants of these epigenetic changes. Questionnaires and breast tissues were collected from healthy women without a history of cancer and undergoing r...

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Autores principales: Dumitrescu, RG, Marian, C, Krishnan, SS, Spear, SL, Kallakury, BVS, Perry, D J, Convit, J R, Seillier-Moiseiwitsch, F, Yang, Y, Freudenheim, JL, Shields, PG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829013/
https://www.ncbi.nlm.nih.gov/pubmed/19799643
http://dx.doi.org/10.1111/j.1582-4934.2009.00924.x
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author Dumitrescu, RG
Marian, C
Krishnan, SS
Spear, SL
Kallakury, BVS
Perry, D J
Convit, J R
Seillier-Moiseiwitsch, F
Yang, Y
Freudenheim, JL
Shields, PG
author_facet Dumitrescu, RG
Marian, C
Krishnan, SS
Spear, SL
Kallakury, BVS
Perry, D J
Convit, J R
Seillier-Moiseiwitsch, F
Yang, Y
Freudenheim, JL
Shields, PG
author_sort Dumitrescu, RG
collection PubMed
description To determine the hypermethylation status of the promoter regions of tumour suppressor genes in breast tissues from healthy women and identify the determinants of these epigenetic changes. Questionnaires and breast tissues were collected from healthy women without a history of cancer and undergoing reduction mammoplasty (N= 141). Methylation for p16(INK4), BRCA1, ERα and RAR-β promoter regions from breast tissues were determined by methylation specific PCR. Associations were examined with chi-square and Fisher’s exact test as well as logistic regression. All statistical tests were two-sided. p16(INK4), BRCA1, ERα and RAR-β hypermethylation were identified in 31%, 17%, 9% and 0% of the women, respectively. Women with BRCA1 hypermethylation had an eight-fold increase in the risk of ERα hypermethylation (P= 0.007). p16(INK4) hypermethylation was present in 28% of African-Americans, but 65% in European-Americans (P= 0.02). There was an increased likelihood of p16(INK4) or BRCA1 hypermethylation for women with family history of cancer (OR 2.3; 95%CI: 1.05–4.85 and OR 5.0; 95%CI: 1.55–15.81, respectively). ERα hypermethylation was associated with family history of breast cancer (OR 6.6; 95%CI: 1.58–27.71). After stratification by race, p16(INK4) in European-Americans and BRCA1 hypermethylation in African-Americans were associated with family history of cancer (OR 3.8; 95%CI: 1.21–12.03 and OR 6.5; 95%CI: 1.33–31.32, respectively). Gene promoter hypermethylation was commonly found in healthy breast tissues from women without cancer, indicating that these events are frequent and early lesions. Race and family history of cancer increase the likelihood of these early events.
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spelling pubmed-38290132014-01-27 Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women Dumitrescu, RG Marian, C Krishnan, SS Spear, SL Kallakury, BVS Perry, D J Convit, J R Seillier-Moiseiwitsch, F Yang, Y Freudenheim, JL Shields, PG J Cell Mol Med Original Articles To determine the hypermethylation status of the promoter regions of tumour suppressor genes in breast tissues from healthy women and identify the determinants of these epigenetic changes. Questionnaires and breast tissues were collected from healthy women without a history of cancer and undergoing reduction mammoplasty (N= 141). Methylation for p16(INK4), BRCA1, ERα and RAR-β promoter regions from breast tissues were determined by methylation specific PCR. Associations were examined with chi-square and Fisher’s exact test as well as logistic regression. All statistical tests were two-sided. p16(INK4), BRCA1, ERα and RAR-β hypermethylation were identified in 31%, 17%, 9% and 0% of the women, respectively. Women with BRCA1 hypermethylation had an eight-fold increase in the risk of ERα hypermethylation (P= 0.007). p16(INK4) hypermethylation was present in 28% of African-Americans, but 65% in European-Americans (P= 0.02). There was an increased likelihood of p16(INK4) or BRCA1 hypermethylation for women with family history of cancer (OR 2.3; 95%CI: 1.05–4.85 and OR 5.0; 95%CI: 1.55–15.81, respectively). ERα hypermethylation was associated with family history of breast cancer (OR 6.6; 95%CI: 1.58–27.71). After stratification by race, p16(INK4) in European-Americans and BRCA1 hypermethylation in African-Americans were associated with family history of cancer (OR 3.8; 95%CI: 1.21–12.03 and OR 6.5; 95%CI: 1.33–31.32, respectively). Gene promoter hypermethylation was commonly found in healthy breast tissues from women without cancer, indicating that these events are frequent and early lesions. Race and family history of cancer increase the likelihood of these early events. Blackwell Publishing Ltd 2010-06 2009-10-03 /pmc/articles/PMC3829013/ /pubmed/19799643 http://dx.doi.org/10.1111/j.1582-4934.2009.00924.x Text en © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Original Articles
Dumitrescu, RG
Marian, C
Krishnan, SS
Spear, SL
Kallakury, BVS
Perry, D J
Convit, J R
Seillier-Moiseiwitsch, F
Yang, Y
Freudenheim, JL
Shields, PG
Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title_full Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title_fullStr Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title_full_unstemmed Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title_short Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
title_sort familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829013/
https://www.ncbi.nlm.nih.gov/pubmed/19799643
http://dx.doi.org/10.1111/j.1582-4934.2009.00924.x
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