Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000

2.50
Hdl Handle:
http://hdl.handle.net/2336/6581
Title:
Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000
Authors:
Tryggvadottir, Laufey; Sigvaldason, Helgi; Olafsdottir, Gudridur H; Jonasson, Jon G; Jonsson, Thorvaldur; Tulinius, Hrafn; Eyfjörd, Jorunn E
Citation:
J. Natl. Cancer Inst. 2006, 98(2):116-22
Issue Date:
18-Jan-2006
Abstract:
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 = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out. CONCLUSIONS: The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.
Description:
To access Publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/2/116

Full metadata record

DC FieldValue Language
dc.contributor.authorTryggvadottir, Laufey-
dc.contributor.authorSigvaldason, Helgi-
dc.contributor.authorOlafsdottir, Gudridur H-
dc.contributor.authorJonasson, Jon G-
dc.contributor.authorJonsson, Thorvaldur-
dc.contributor.authorTulinius, Hrafn-
dc.contributor.authorEyfjörd, Jorunn E-
dc.date.accessioned2006-12-15T12:22:56Z-
dc.date.available2006-12-15T12:22:56Z-
dc.date.issued2006-01-18-
dc.date.submitted2006-12-15-
dc.identifier.citationJ. Natl. Cancer Inst. 2006, 98(2):116-22en
dc.identifier.issn1460-2105-
dc.identifier.pmid16418514-
dc.identifier.doi10.1093/jnci/djj012-
dc.identifier.urihttp://hdl.handle.net/2336/6581-
dc.descriptionTo access Publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: 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 = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out. CONCLUSIONS: The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urlhttp://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/2/116en
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshBreast Neoplasmsen
dc.subject.meshFemaleen
dc.subject.meshFounder Effecten
dc.subject.meshGenes, BRCA2en
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHeterozygoteen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshIncidenceen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshPenetranceen
dc.subject.meshPoisson Distributionen
dc.subject.meshRegistriesen
dc.subject.meshRisk Assessmenten
dc.titlePopulation-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000en
dc.typeArticleen
dc.identifier.journalJournal of the National Cancer Instituteen
dc.format.digYES-

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