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A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland

BACKGROUND: Germline mutations of the CHEK2 gene have been reported to be associated with breast cancer. In this study, we analyzed the association of CHEK2 mutations with the risk of development of breast cancer in women of North-Central Poland. METHODS: 420 women with breast cancer and 435 control...

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Autores principales: Bąk, Aneta, Janiszewska, Hanna, Junkiert-Czarnecka, Anna, Heise, Marta, Pilarska-Deltow, Maria, Laskowski, Ryszard, Pasińska, Magdalena, Haus, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991918/
https://www.ncbi.nlm.nih.gov/pubmed/24713400
http://dx.doi.org/10.1186/1897-4287-12-10
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author Bąk, Aneta
Janiszewska, Hanna
Junkiert-Czarnecka, Anna
Heise, Marta
Pilarska-Deltow, Maria
Laskowski, Ryszard
Pasińska, Magdalena
Haus, Olga
author_facet Bąk, Aneta
Janiszewska, Hanna
Junkiert-Czarnecka, Anna
Heise, Marta
Pilarska-Deltow, Maria
Laskowski, Ryszard
Pasińska, Magdalena
Haus, Olga
author_sort Bąk, Aneta
collection PubMed
description BACKGROUND: Germline mutations of the CHEK2 gene have been reported to be associated with breast cancer. In this study, we analyzed the association of CHEK2 mutations with the risk of development of breast cancer in women of North-Central Poland. METHODS: 420 women with breast cancer and 435 controls were tested for three protein truncating (IVS2 + 1G > A, 1100delC, del5395) and one missense (I157T) CHEK2 mutation. IVS2 + 1G > A and I157T mutations were identified by RFLP-PCR, 1100delC variant was analyzed using an ASO-PCR and del5395 mutation by multiplex-PCR. The statistical tests: the odds ratio (OR) and Fisher’s exact test were used. RESULTS: In 33 out of 420 (7.9%) women consecutively diagnosed with breast cancer, we detected one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2 + 1G > A or del5395. Together they were not associated with the increased risk of breast cancer (North-Central control group: OR = 1.6, p = 0.124; the general Polish population: OR = 1.4, p = 0.109). This association was only seen for IVS2 + 1G > A mutation (OR = 3.0; p = 0.039). One of the three truncating CHEK2 mutations (IVS2 + 1G > A, 1100delC, del5395) was present in 9 of 420 women diagnosed with breast cancer (2.1%) and in 4 of 121 women (3.3%) with a history of breast cancer in a first- and/or second- degree relatives. Together they were associated with the increased risk of disease in these groups, compared to the general Polish population (OR = 2.1, p = 0.053 and OR = 3.2; p = 0.044, respectively). I157T mutation was detected in 25 of 420 women diagnosed with breast cancer (6.0%) and in 8 of 121 women (6.6%) with a history of breast cancer in first- and/or second- degree relatives. The prevalance of I157T mutation was 4.1% (18/435) in North-Central control group and 4.8% (265/5.496) in the general Polish population. However it was not associated with an increased risk of breast cancer. CONCLUSION: Obtained results suggest that CHEK2 mutations could potentially contribute to the susceptibility to breast cancer. The germline mutations of CHEK2, especially the truncating ones confer low-penetrance breast cancer predisposition that contribute significantly to familial clustering of breast cancer at the population level.
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spelling pubmed-39919182014-04-20 A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland Bąk, Aneta Janiszewska, Hanna Junkiert-Czarnecka, Anna Heise, Marta Pilarska-Deltow, Maria Laskowski, Ryszard Pasińska, Magdalena Haus, Olga Hered Cancer Clin Pract Research BACKGROUND: Germline mutations of the CHEK2 gene have been reported to be associated with breast cancer. In this study, we analyzed the association of CHEK2 mutations with the risk of development of breast cancer in women of North-Central Poland. METHODS: 420 women with breast cancer and 435 controls were tested for three protein truncating (IVS2 + 1G > A, 1100delC, del5395) and one missense (I157T) CHEK2 mutation. IVS2 + 1G > A and I157T mutations were identified by RFLP-PCR, 1100delC variant was analyzed using an ASO-PCR and del5395 mutation by multiplex-PCR. The statistical tests: the odds ratio (OR) and Fisher’s exact test were used. RESULTS: In 33 out of 420 (7.9%) women consecutively diagnosed with breast cancer, we detected one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2 + 1G > A or del5395. Together they were not associated with the increased risk of breast cancer (North-Central control group: OR = 1.6, p = 0.124; the general Polish population: OR = 1.4, p = 0.109). This association was only seen for IVS2 + 1G > A mutation (OR = 3.0; p = 0.039). One of the three truncating CHEK2 mutations (IVS2 + 1G > A, 1100delC, del5395) was present in 9 of 420 women diagnosed with breast cancer (2.1%) and in 4 of 121 women (3.3%) with a history of breast cancer in a first- and/or second- degree relatives. Together they were associated with the increased risk of disease in these groups, compared to the general Polish population (OR = 2.1, p = 0.053 and OR = 3.2; p = 0.044, respectively). I157T mutation was detected in 25 of 420 women diagnosed with breast cancer (6.0%) and in 8 of 121 women (6.6%) with a history of breast cancer in first- and/or second- degree relatives. The prevalance of I157T mutation was 4.1% (18/435) in North-Central control group and 4.8% (265/5.496) in the general Polish population. However it was not associated with an increased risk of breast cancer. CONCLUSION: Obtained results suggest that CHEK2 mutations could potentially contribute to the susceptibility to breast cancer. The germline mutations of CHEK2, especially the truncating ones confer low-penetrance breast cancer predisposition that contribute significantly to familial clustering of breast cancer at the population level. BioMed Central 2014-04-08 /pmc/articles/PMC3991918/ /pubmed/24713400 http://dx.doi.org/10.1186/1897-4287-12-10 Text en Copyright © 2014 Bąk et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bąk, Aneta
Janiszewska, Hanna
Junkiert-Czarnecka, Anna
Heise, Marta
Pilarska-Deltow, Maria
Laskowski, Ryszard
Pasińska, Magdalena
Haus, Olga
A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title_full A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title_fullStr A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title_full_unstemmed A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title_short A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland
title_sort risk of breast cancer in women - carriers of constitutional chek2 gene mutations, originating from the north - central poland
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991918/
https://www.ncbi.nlm.nih.gov/pubmed/24713400
http://dx.doi.org/10.1186/1897-4287-12-10
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