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ATM polymorphisms as risk factors for prostate cancer development
The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2004
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364767/ https://www.ncbi.nlm.nih.gov/pubmed/15280931 http://dx.doi.org/10.1038/sj.bjc.6602007 |
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author | Angèle, S Falconer, A Edwards, S M Dörk, T Bremer, M Moullan, N Chapot, B Muir, K Houlston, R Norman, A R Bullock, S Hope, Q Meitz, J Dearnaley, D Dowe, A Southgate, C Ardern-Jones, A Easton, D F Eeles, R A Hall, J |
author_facet | Angèle, S Falconer, A Edwards, S M Dörk, T Bremer, M Moullan, N Chapot, B Muir, K Houlston, R Norman, A R Bullock, S Hope, Q Meitz, J Dearnaley, D Dowe, A Southgate, C Ardern-Jones, A Easton, D F Eeles, R A Hall, J |
author_sort | Angèle, S |
collection | PubMed |
description | The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17–3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk. |
format | Text |
id | pubmed-2364767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23647672009-09-10 ATM polymorphisms as risk factors for prostate cancer development Angèle, S Falconer, A Edwards, S M Dörk, T Bremer, M Moullan, N Chapot, B Muir, K Houlston, R Norman, A R Bullock, S Hope, Q Meitz, J Dearnaley, D Dowe, A Southgate, C Ardern-Jones, A Easton, D F Eeles, R A Hall, J Br J Cancer Genetics and Genomics The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17–3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk. Nature Publishing Group 2004-08-16 2004-07-27 /pmc/articles/PMC2364767/ /pubmed/15280931 http://dx.doi.org/10.1038/sj.bjc.6602007 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Genetics and Genomics Angèle, S Falconer, A Edwards, S M Dörk, T Bremer, M Moullan, N Chapot, B Muir, K Houlston, R Norman, A R Bullock, S Hope, Q Meitz, J Dearnaley, D Dowe, A Southgate, C Ardern-Jones, A Easton, D F Eeles, R A Hall, J ATM polymorphisms as risk factors for prostate cancer development |
title | ATM polymorphisms as risk factors for prostate cancer development |
title_full | ATM polymorphisms as risk factors for prostate cancer development |
title_fullStr | ATM polymorphisms as risk factors for prostate cancer development |
title_full_unstemmed | ATM polymorphisms as risk factors for prostate cancer development |
title_short | ATM polymorphisms as risk factors for prostate cancer development |
title_sort | atm polymorphisms as risk factors for prostate cancer development |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364767/ https://www.ncbi.nlm.nih.gov/pubmed/15280931 http://dx.doi.org/10.1038/sj.bjc.6602007 |
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