Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000
To access Publisher full text version of this article. Please click on the hyperlink in Additional Links field BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed...
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Online Access: | http://hdl.handle.net/2336/6581 https://doi.org/10.1093/jnci/djj012 |
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/6581 2023-05-15T16:49:39+02:00 Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 Tryggvadottir, Laufey Sigvaldason, Helgi Olafsdottir, Gudridur H Jonasson, Jon G Jonsson, Thorvaldur Tulinius, Hrafn Eyfjörd, Jorunn E 2006-12-15 YES http://hdl.handle.net/2336/6581 https://doi.org/10.1093/jnci/djj012 en eng Oxford University Press http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/2/116 J. Natl. Cancer Inst. 2006, 98(2):116-22 1460-2105 16418514 doi:10.1093/jnci/djj012 http://hdl.handle.net/2336/6581 Journal of the National Cancer Institute Adult Aged Breast Neoplasms Female Founder Effect Genes BRCA2 Genetic Predisposition to Disease Heterozygote Humans Iceland Incidence Middle Aged Mutation Penetrance Poisson Distribution Registries Risk Assessment Article 2006 ftlandspitaliuni https://doi.org/10.1093/jnci/djj012 2022-05-29T08:20:55Z To access Publisher full text version of this article. Please click on the hyperlink in Additional Links field BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5. METHODS: Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided. RESULTS: Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = ... Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive JNCI: Journal of the National Cancer Institute 98 2 116 122 |
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Hirsla - Landspítali University Hospital research archive |
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ftlandspitaliuni |
language |
English |
topic |
Adult Aged Breast Neoplasms Female Founder Effect Genes BRCA2 Genetic Predisposition to Disease Heterozygote Humans Iceland Incidence Middle Aged Mutation Penetrance Poisson Distribution Registries Risk Assessment |
spellingShingle |
Adult Aged Breast Neoplasms Female Founder Effect Genes BRCA2 Genetic Predisposition to Disease Heterozygote Humans Iceland Incidence Middle Aged Mutation Penetrance Poisson Distribution Registries Risk Assessment Tryggvadottir, Laufey Sigvaldason, Helgi Olafsdottir, Gudridur H Jonasson, Jon G Jonsson, Thorvaldur Tulinius, Hrafn Eyfjörd, Jorunn E Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
topic_facet |
Adult Aged Breast Neoplasms Female Founder Effect Genes BRCA2 Genetic Predisposition to Disease Heterozygote Humans Iceland Incidence Middle Aged Mutation Penetrance Poisson Distribution Registries Risk Assessment |
description |
To access Publisher full text version of this article. Please click on the hyperlink in Additional Links field BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5. METHODS: Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided. RESULTS: Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = ... |
format |
Article in Journal/Newspaper |
author |
Tryggvadottir, Laufey Sigvaldason, Helgi Olafsdottir, Gudridur H Jonasson, Jon G Jonsson, Thorvaldur Tulinius, Hrafn Eyfjörd, Jorunn E |
author_facet |
Tryggvadottir, Laufey Sigvaldason, Helgi Olafsdottir, Gudridur H Jonasson, Jon G Jonsson, Thorvaldur Tulinius, Hrafn Eyfjörd, Jorunn E |
author_sort |
Tryggvadottir, Laufey |
title |
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
title_short |
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
title_full |
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
title_fullStr |
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
title_full_unstemmed |
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000 |
title_sort |
population-based study of changing breast cancer risk in icelandic brca2 mutation carriers, 1920-2000 |
publisher |
Oxford University Press |
publishDate |
2006 |
url |
http://hdl.handle.net/2336/6581 https://doi.org/10.1093/jnci/djj012 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/2/116 J. Natl. Cancer Inst. 2006, 98(2):116-22 1460-2105 16418514 doi:10.1093/jnci/djj012 http://hdl.handle.net/2336/6581 Journal of the National Cancer Institute |
op_doi |
https://doi.org/10.1093/jnci/djj012 |
container_title |
JNCI: Journal of the National Cancer Institute |
container_volume |
98 |
container_issue |
2 |
container_start_page |
116 |
op_container_end_page |
122 |
_version_ |
1766039789943914496 |