The association between cancer family history and ovarian cancer risk in BRCA1/2 mutation carriers: can it be explained by the mutation position?

HEBON

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

This observational study aimed to investigate whether the reported association between family history (FH) of breast cancer (BC) or ovarian cancer (OC) and OC risks in BRCA1/2 mutation carriers can be explained by mutation position on the gene. In total, 3310 female BRCA1/2 mutation carriers participating in a nationwide prospective cohort (Hereditary Breast and Ovarian Cancer in the Netherlands) were included. FH was classified according to cancer occurrence in first-degree relatives (BC only, OC only, both, neither) and mutations were classified according to their position on the gene (OC cluster region (OCCR), BC cluster region, neither). The main outcome was OC occurrence. Cox proportional-hazard models were applied to investigate the association between FH and OC risks before and after adjusting for mutation position. Of all women included, 202 were diagnosed with OC. A BC-only FH tended to be associated with lower OC risks when compared with a FH without BC/OC (HR: 0.79, 95% CI: 0.52-1.17; HR: 0.59, 95% CI: 0.33-1.07 for BRCA1 and BRCA2, respectively) while an OC-only FH tended to be associated with higher risks (HR: 1.58, 95% CI: 0.90-2.77; HR: 1.75, 95% CI: 0.70-4.37 for BRCA1 and BRCA2, respectively). After adjusting for mutation position, association between FH and OC risks was slightly smaller in magnitude (HR: 0.85, 95% CI: 0.55-1.30; HR: 0.64, 95% CI: 0.34-1.21 for BC-only FH in BRCA1 and BRCA2, respectively; HR: 1.46, 95% CI: 0.80-2.68; HR: 1.49, 95% CI: 0.44-4.02 for OC-only FH in BRCA1 and BRCA2, respectively), indicating that mutation position explains only part of the association. Considering the magnitude of the observed trend, we do not believe FH should be used to change counseling regarding OC prevention.

Original languageEnglish
Pages (from-to)848-857
Number of pages10
JournalEuropean Journal of Human Genetics
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 2018

Cite this

@article{0f8a73c81bf546c28cab90779e5cdb79,
title = "The association between cancer family history and ovarian cancer risk in BRCA1/2 mutation carriers: can it be explained by the mutation position?",
abstract = "This observational study aimed to investigate whether the reported association between family history (FH) of breast cancer (BC) or ovarian cancer (OC) and OC risks in BRCA1/2 mutation carriers can be explained by mutation position on the gene. In total, 3310 female BRCA1/2 mutation carriers participating in a nationwide prospective cohort (Hereditary Breast and Ovarian Cancer in the Netherlands) were included. FH was classified according to cancer occurrence in first-degree relatives (BC only, OC only, both, neither) and mutations were classified according to their position on the gene (OC cluster region (OCCR), BC cluster region, neither). The main outcome was OC occurrence. Cox proportional-hazard models were applied to investigate the association between FH and OC risks before and after adjusting for mutation position. Of all women included, 202 were diagnosed with OC. A BC-only FH tended to be associated with lower OC risks when compared with a FH without BC/OC (HR: 0.79, 95{\%} CI: 0.52-1.17; HR: 0.59, 95{\%} CI: 0.33-1.07 for BRCA1 and BRCA2, respectively) while an OC-only FH tended to be associated with higher risks (HR: 1.58, 95{\%} CI: 0.90-2.77; HR: 1.75, 95{\%} CI: 0.70-4.37 for BRCA1 and BRCA2, respectively). After adjusting for mutation position, association between FH and OC risks was slightly smaller in magnitude (HR: 0.85, 95{\%} CI: 0.55-1.30; HR: 0.64, 95{\%} CI: 0.34-1.21 for BC-only FH in BRCA1 and BRCA2, respectively; HR: 1.46, 95{\%} CI: 0.80-2.68; HR: 1.49, 95{\%} CI: 0.44-4.02 for OC-only FH in BRCA1 and BRCA2, respectively), indicating that mutation position explains only part of the association. Considering the magnitude of the observed trend, we do not believe FH should be used to change counseling regarding OC prevention.",
author = "HEBON and Natalia Teixeira and {van der Hout}, Annemieke and Oosterwijk, {Jan C} and Vos, {Janet R} and Peter Devilee and {van Engelen}, Klaartje and Hanne Meijers-Heijboer and {van der Luijt}, {Rob B} and Mieke Kriege and Mensenkamp, {Arjen R} and Rookus, {Matti A} and {van Roozendaal}, {Kees E} and Mourits, {Marian J E} and {de Bock}, {Geertruida H}",
year = "2018",
month = "6",
doi = "10.1038/s41431-018-0111-9",
language = "English",
volume = "26",
pages = "848--857",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",
number = "6",

}

The association between cancer family history and ovarian cancer risk in BRCA1/2 mutation carriers : can it be explained by the mutation position? / HEBON.

In: European Journal of Human Genetics, Vol. 26, No. 6, 06.2018, p. 848-857.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The association between cancer family history and ovarian cancer risk in BRCA1/2 mutation carriers

T2 - can it be explained by the mutation position?

AU - HEBON

AU - Teixeira, Natalia

AU - van der Hout, Annemieke

AU - Oosterwijk, Jan C

AU - Vos, Janet R

AU - Devilee, Peter

AU - van Engelen, Klaartje

AU - Meijers-Heijboer, Hanne

AU - van der Luijt, Rob B

AU - Kriege, Mieke

AU - Mensenkamp, Arjen R

AU - Rookus, Matti A

AU - van Roozendaal, Kees E

AU - Mourits, Marian J E

AU - de Bock, Geertruida H

PY - 2018/6

Y1 - 2018/6

N2 - This observational study aimed to investigate whether the reported association between family history (FH) of breast cancer (BC) or ovarian cancer (OC) and OC risks in BRCA1/2 mutation carriers can be explained by mutation position on the gene. In total, 3310 female BRCA1/2 mutation carriers participating in a nationwide prospective cohort (Hereditary Breast and Ovarian Cancer in the Netherlands) were included. FH was classified according to cancer occurrence in first-degree relatives (BC only, OC only, both, neither) and mutations were classified according to their position on the gene (OC cluster region (OCCR), BC cluster region, neither). The main outcome was OC occurrence. Cox proportional-hazard models were applied to investigate the association between FH and OC risks before and after adjusting for mutation position. Of all women included, 202 were diagnosed with OC. A BC-only FH tended to be associated with lower OC risks when compared with a FH without BC/OC (HR: 0.79, 95% CI: 0.52-1.17; HR: 0.59, 95% CI: 0.33-1.07 for BRCA1 and BRCA2, respectively) while an OC-only FH tended to be associated with higher risks (HR: 1.58, 95% CI: 0.90-2.77; HR: 1.75, 95% CI: 0.70-4.37 for BRCA1 and BRCA2, respectively). After adjusting for mutation position, association between FH and OC risks was slightly smaller in magnitude (HR: 0.85, 95% CI: 0.55-1.30; HR: 0.64, 95% CI: 0.34-1.21 for BC-only FH in BRCA1 and BRCA2, respectively; HR: 1.46, 95% CI: 0.80-2.68; HR: 1.49, 95% CI: 0.44-4.02 for OC-only FH in BRCA1 and BRCA2, respectively), indicating that mutation position explains only part of the association. Considering the magnitude of the observed trend, we do not believe FH should be used to change counseling regarding OC prevention.

AB - This observational study aimed to investigate whether the reported association between family history (FH) of breast cancer (BC) or ovarian cancer (OC) and OC risks in BRCA1/2 mutation carriers can be explained by mutation position on the gene. In total, 3310 female BRCA1/2 mutation carriers participating in a nationwide prospective cohort (Hereditary Breast and Ovarian Cancer in the Netherlands) were included. FH was classified according to cancer occurrence in first-degree relatives (BC only, OC only, both, neither) and mutations were classified according to their position on the gene (OC cluster region (OCCR), BC cluster region, neither). The main outcome was OC occurrence. Cox proportional-hazard models were applied to investigate the association between FH and OC risks before and after adjusting for mutation position. Of all women included, 202 were diagnosed with OC. A BC-only FH tended to be associated with lower OC risks when compared with a FH without BC/OC (HR: 0.79, 95% CI: 0.52-1.17; HR: 0.59, 95% CI: 0.33-1.07 for BRCA1 and BRCA2, respectively) while an OC-only FH tended to be associated with higher risks (HR: 1.58, 95% CI: 0.90-2.77; HR: 1.75, 95% CI: 0.70-4.37 for BRCA1 and BRCA2, respectively). After adjusting for mutation position, association between FH and OC risks was slightly smaller in magnitude (HR: 0.85, 95% CI: 0.55-1.30; HR: 0.64, 95% CI: 0.34-1.21 for BC-only FH in BRCA1 and BRCA2, respectively; HR: 1.46, 95% CI: 0.80-2.68; HR: 1.49, 95% CI: 0.44-4.02 for OC-only FH in BRCA1 and BRCA2, respectively), indicating that mutation position explains only part of the association. Considering the magnitude of the observed trend, we do not believe FH should be used to change counseling regarding OC prevention.

U2 - 10.1038/s41431-018-0111-9

DO - 10.1038/s41431-018-0111-9

M3 - Article

VL - 26

SP - 848

EP - 857

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 6

ER -