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ATM variants and cancer risk in breast cancer patients from Southern Finland

BACKGROUND: Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D185...

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Autores principales: Tommiska, Johanna, Jansen, Laila, Kilpivaara, Outi, Edvardsen, Hege, Kristensen, Vessela, Tamminen, Anitta, Aittomäki, Kristiina, Blomqvist, Carl, Børresen-Dale, Anne-Lise, Nevanlinna, Heli
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592307/
https://www.ncbi.nlm.nih.gov/pubmed/16914028
http://dx.doi.org/10.1186/1471-2407-6-209
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author Tommiska, Johanna
Jansen, Laila
Kilpivaara, Outi
Edvardsen, Hege
Kristensen, Vessela
Tamminen, Anitta
Aittomäki, Kristiina
Blomqvist, Carl
Børresen-Dale, Anne-Lise
Nevanlinna, Heli
author_facet Tommiska, Johanna
Jansen, Laila
Kilpivaara, Outi
Edvardsen, Hege
Kristensen, Vessela
Tamminen, Anitta
Aittomäki, Kristiina
Blomqvist, Carl
Børresen-Dale, Anne-Lise
Nevanlinna, Heli
author_sort Tommiska, Johanna
collection PubMed
description BACKGROUND: Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D1853N) variant, was suggested to associate with bilateral breast cancer among familial breast cancer patients from Northern Finland. We have here evaluated the 5557G>A and ivs38-8T>C variants in an extensive case-control association analysis. We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. METHODS: Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls. RESULTS: Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls. CONCLUSION: Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with increased breast cancer risk or with bilateral breast cancer.
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spelling pubmed-15923072006-10-06 ATM variants and cancer risk in breast cancer patients from Southern Finland Tommiska, Johanna Jansen, Laila Kilpivaara, Outi Edvardsen, Hege Kristensen, Vessela Tamminen, Anitta Aittomäki, Kristiina Blomqvist, Carl Børresen-Dale, Anne-Lise Nevanlinna, Heli BMC Cancer Research Article BACKGROUND: Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D1853N) variant, was suggested to associate with bilateral breast cancer among familial breast cancer patients from Northern Finland. We have here evaluated the 5557G>A and ivs38-8T>C variants in an extensive case-control association analysis. We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. METHODS: Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls. RESULTS: Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls. CONCLUSION: Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with increased breast cancer risk or with bilateral breast cancer. BioMed Central 2006-08-16 /pmc/articles/PMC1592307/ /pubmed/16914028 http://dx.doi.org/10.1186/1471-2407-6-209 Text en Copyright © 2006 Tommiska 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 cited.
spellingShingle Research Article
Tommiska, Johanna
Jansen, Laila
Kilpivaara, Outi
Edvardsen, Hege
Kristensen, Vessela
Tamminen, Anitta
Aittomäki, Kristiina
Blomqvist, Carl
Børresen-Dale, Anne-Lise
Nevanlinna, Heli
ATM variants and cancer risk in breast cancer patients from Southern Finland
title ATM variants and cancer risk in breast cancer patients from Southern Finland
title_full ATM variants and cancer risk in breast cancer patients from Southern Finland
title_fullStr ATM variants and cancer risk in breast cancer patients from Southern Finland
title_full_unstemmed ATM variants and cancer risk in breast cancer patients from Southern Finland
title_short ATM variants and cancer risk in breast cancer patients from Southern Finland
title_sort atm variants and cancer risk in breast cancer patients from southern finland
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592307/
https://www.ncbi.nlm.nih.gov/pubmed/16914028
http://dx.doi.org/10.1186/1471-2407-6-209
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