The University of Southampton
University of Southampton Institutional Repository

Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers

Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers
Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers
BACKGROUND: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies.

METHODS: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated.

RESULTS: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk.

CONCLUSION: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers.

IMPACT: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.
1032-1038
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Marquart, Louise
61b90f9b-c361-4ef9-97e1-8125d309aabd
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
Healey, Sue
5d595192-5381-464d-85cc-71ad09a05065
Sinilnikova, Olga
a2fdd043-1545-4ffb-9299-3173b9b9d815
Wan, Fei
8d2bfe7f-a2bc-4e3b-976c-7792d1d1760b
Chen, Xiaoqing
ee420c6c-2134-49d2-8238-514d837c725f
Beesley, Jonathan
0ec7ea7e-d634-48f5-9a1a-89158c82597d
Singer, Christian F.
3ac2e574-0627-4715-ac4a-8ab7edcc3851
Dressler, Anne-Catharine
918e602f-2f0c-41fd-b31a-5b0d4b64d3a6
Gschwantler-Kaulich, Daphne
08c03d3a-2158-4f5b-bee3-3c5fbd301053
Blum, Joanne L.
c9cd10b1-c415-4968-981e-06d194c00444
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Weitzel, Jeff
a407f17c-c5b3-4db0-9dec-eb71f35d9825
Lynch, Henry
e0950da0-bf3d-4f24-9ce5-fbe60e880b3f
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Peock, Susan
7e420471-9ee5-4a07-9536-bfdc4c6f1297
Cook, Margaret
b693d851-afb5-4cf6-ad02-4bb9169b5fe3
Oliver, Clare T.
f0c81ad8-7e4f-4516-9c6e-1c5c547b39de
Frost, Debra
658754fc-a2bb-4174-9b9d-14e5331ebeb8
Conroy, Don
928c9b47-b4b4-42d0-bddc-edae4cbd517e
Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Lalloo, Fiona
d7ac29ee-10db-49a5-af3c-265b6d1c113d
Eeles, Ros
1101f5dc-f8ae-4102-99fb-f814695e5f9c
Izatt, Louise
5d6201a8-8a56-4923-ac9d-75dca6be0a40
Davidson, Rosemarie
81692cd9-0a70-4a01-a68f-8eb623f0fbe0
Chu, Carol
156d1c39-a711-4edf-871c-f528e47b25eb
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Selkirk, Christina G.
b523f781-a4be-4663-98c4-088895dd842f
Daly, Mary
fa76e783-83e7-41a1-9e34-84dee1b57102
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Stoppa-Lyonnet, Dominique
c110a3bd-17a1-4b82-9b32-75728172bfc5
Sinilnikova, Olga M.
17bb19c7-8db3-48e3-8630-0c9a78a2e1a4
Buecher, Bruno
0f1a3060-ebe8-477b-b91b-aa842475a7f5
Belotti, Muriel
80dfd1e9-51bc-4ebb-bba9-849334509afb
Mazoyer, Sylvie
6e0e32e4-7d0e-4c7c-bd80-d221d53af542
Barjhoux, Laure
e5969462-17f0-4bed-b904-e30f6d246d5d
Verny-Pierre, Carole
926dd608-8263-4ece-840e-094b8be474df
Lasset, Christine
b16ee5ce-49c4-4c51-b793-9d2b3a3d314a
Dreyfus, Hélène
e2566ad7-4fd7-4422-be53-7eb6b4fce32b
Pujol, Pascal
c2d9280d-450d-4000-95bf-2d3d81ba0a15
Collonge-Rame, Marie-Agnès
49d002a8-af2e-4d49-801f-3d31f31c1962
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Verhoef, Senno
938f6328-60a4-4848-a436-349bfc036c6f
Kriege, Mieke
515c3c22-eedc-44b2-ae00-24ce06e6e95b
Hoogerbrugge, Nicoline
8d257648-db15-4549-af48-23b7d8d6e42f
Ausems, Margaret G. E. M.
d8b9e13c-205d-4506-8466-adb131a91ec3
van Os, Theo A.
1bc277ed-8e74-4571-9bc2-1ac9ec26369c
Wijnen, Juul
1556ff67-a692-4d20-b2a8-d0869985558e
Devilee, Peter
70de16eb-ec65-4e3e-b8f7-6333896e213f
Meijers-Heijboer, Hanne E. J.
294ed75a-04e3-453c-8601-0f9d2efefce6
Blok, Marinus J.
0fe408b6-18f4-46f6-9b69-f42b8b1f6e06
Heikkinen, Tuomas
0c6ae2e7-0ef1-43e0-9a7b-92d9354e6f10
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Lubinski, Jan
e7a9709c-36b3-44ed-a5e0-675177ca3d51
Huzarski, Tomasz
66e38515-375a-430f-9528-41912816378d
Byrski, Tomasz
9cb401e1-f220-4cab-b2c6-566bd3877c24
Durocher, Francine
c888e397-4476-4482-8f4a-37f72a380ef8
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Lindor, Noralene M.
93b0a2c7-d98b-4535-9478-f149f302e2f5
Wang, Xianshu
5c376f01-823c-4228-bd76-414a181fa3eb
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Domchek, Susan
df50a114-d9f2-4796-934d-6344bbac5637
Nathanson, Kate
ee357885-a2c6-47a5-8498-c26da1a4470f
Caligo, M. A.
1b57fa11-2039-404a-a80c-0f410e229e85
Jernstrom, Helena
964d4598-b858-4ef8-86e8-fd8d868f33de
Liljegren, Annelie
2bb446db-228b-4e61-91cc-655d47196ac1
Ehrencrona, Hans
3bf9759a-7b66-4492-833a-db923bc49324
Karlsson, Per
cf6072fc-3103-402a-9271-2c37bdeee52d
Ganz, Patricia A.
e7573e53-13b2-4291-80d8-a59249b827fe
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Tomlinson, Gail
abec81c2-80a5-424c-9c69-764157863d48
Neuhausen, Susan
347a965a-60c6-4040-9c04-014f30a25df4
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Rebbeck, Timothy R.
017e04fa-fcd5-48d2-89f5-2e05f4c2091a
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Marquart, Louise
61b90f9b-c361-4ef9-97e1-8125d309aabd
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
Healey, Sue
5d595192-5381-464d-85cc-71ad09a05065
Sinilnikova, Olga
a2fdd043-1545-4ffb-9299-3173b9b9d815
Wan, Fei
8d2bfe7f-a2bc-4e3b-976c-7792d1d1760b
Chen, Xiaoqing
ee420c6c-2134-49d2-8238-514d837c725f
Beesley, Jonathan
0ec7ea7e-d634-48f5-9a1a-89158c82597d
Singer, Christian F.
3ac2e574-0627-4715-ac4a-8ab7edcc3851
Dressler, Anne-Catharine
918e602f-2f0c-41fd-b31a-5b0d4b64d3a6
Gschwantler-Kaulich, Daphne
08c03d3a-2158-4f5b-bee3-3c5fbd301053
Blum, Joanne L.
c9cd10b1-c415-4968-981e-06d194c00444
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Weitzel, Jeff
a407f17c-c5b3-4db0-9dec-eb71f35d9825
Lynch, Henry
e0950da0-bf3d-4f24-9ce5-fbe60e880b3f
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Peock, Susan
7e420471-9ee5-4a07-9536-bfdc4c6f1297
Cook, Margaret
b693d851-afb5-4cf6-ad02-4bb9169b5fe3
Oliver, Clare T.
f0c81ad8-7e4f-4516-9c6e-1c5c547b39de
Frost, Debra
658754fc-a2bb-4174-9b9d-14e5331ebeb8
Conroy, Don
928c9b47-b4b4-42d0-bddc-edae4cbd517e
Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Lalloo, Fiona
d7ac29ee-10db-49a5-af3c-265b6d1c113d
Eeles, Ros
1101f5dc-f8ae-4102-99fb-f814695e5f9c
Izatt, Louise
5d6201a8-8a56-4923-ac9d-75dca6be0a40
Davidson, Rosemarie
81692cd9-0a70-4a01-a68f-8eb623f0fbe0
Chu, Carol
156d1c39-a711-4edf-871c-f528e47b25eb
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Selkirk, Christina G.
b523f781-a4be-4663-98c4-088895dd842f
Daly, Mary
fa76e783-83e7-41a1-9e34-84dee1b57102
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Stoppa-Lyonnet, Dominique
c110a3bd-17a1-4b82-9b32-75728172bfc5
Sinilnikova, Olga M.
17bb19c7-8db3-48e3-8630-0c9a78a2e1a4
Buecher, Bruno
0f1a3060-ebe8-477b-b91b-aa842475a7f5
Belotti, Muriel
80dfd1e9-51bc-4ebb-bba9-849334509afb
Mazoyer, Sylvie
6e0e32e4-7d0e-4c7c-bd80-d221d53af542
Barjhoux, Laure
e5969462-17f0-4bed-b904-e30f6d246d5d
Verny-Pierre, Carole
926dd608-8263-4ece-840e-094b8be474df
Lasset, Christine
b16ee5ce-49c4-4c51-b793-9d2b3a3d314a
Dreyfus, Hélène
e2566ad7-4fd7-4422-be53-7eb6b4fce32b
Pujol, Pascal
c2d9280d-450d-4000-95bf-2d3d81ba0a15
Collonge-Rame, Marie-Agnès
49d002a8-af2e-4d49-801f-3d31f31c1962
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Verhoef, Senno
938f6328-60a4-4848-a436-349bfc036c6f
Kriege, Mieke
515c3c22-eedc-44b2-ae00-24ce06e6e95b
Hoogerbrugge, Nicoline
8d257648-db15-4549-af48-23b7d8d6e42f
Ausems, Margaret G. E. M.
d8b9e13c-205d-4506-8466-adb131a91ec3
van Os, Theo A.
1bc277ed-8e74-4571-9bc2-1ac9ec26369c
Wijnen, Juul
1556ff67-a692-4d20-b2a8-d0869985558e
Devilee, Peter
70de16eb-ec65-4e3e-b8f7-6333896e213f
Meijers-Heijboer, Hanne E. J.
294ed75a-04e3-453c-8601-0f9d2efefce6
Blok, Marinus J.
0fe408b6-18f4-46f6-9b69-f42b8b1f6e06
Heikkinen, Tuomas
0c6ae2e7-0ef1-43e0-9a7b-92d9354e6f10
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Lubinski, Jan
e7a9709c-36b3-44ed-a5e0-675177ca3d51
Huzarski, Tomasz
66e38515-375a-430f-9528-41912816378d
Byrski, Tomasz
9cb401e1-f220-4cab-b2c6-566bd3877c24
Durocher, Francine
c888e397-4476-4482-8f4a-37f72a380ef8
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Lindor, Noralene M.
93b0a2c7-d98b-4535-9478-f149f302e2f5
Wang, Xianshu
5c376f01-823c-4228-bd76-414a181fa3eb
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Domchek, Susan
df50a114-d9f2-4796-934d-6344bbac5637
Nathanson, Kate
ee357885-a2c6-47a5-8498-c26da1a4470f
Caligo, M. A.
1b57fa11-2039-404a-a80c-0f410e229e85
Jernstrom, Helena
964d4598-b858-4ef8-86e8-fd8d868f33de
Liljegren, Annelie
2bb446db-228b-4e61-91cc-655d47196ac1
Ehrencrona, Hans
3bf9759a-7b66-4492-833a-db923bc49324
Karlsson, Per
cf6072fc-3103-402a-9271-2c37bdeee52d
Ganz, Patricia A.
e7573e53-13b2-4291-80d8-a59249b827fe
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Tomlinson, Gail
abec81c2-80a5-424c-9c69-764157863d48
Neuhausen, Susan
347a965a-60c6-4040-9c04-014f30a25df4
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Rebbeck, Timothy R.
017e04fa-fcd5-48d2-89f5-2e05f4c2091a

Spurdle, Amanda B., Marquart, Louise, McGuffog, Lesley, Healey, Sue, Sinilnikova, Olga, Wan, Fei, Chen, Xiaoqing, Beesley, Jonathan, Singer, Christian F., Dressler, Anne-Catharine, Gschwantler-Kaulich, Daphne, Blum, Joanne L., Tung, Nadine, Weitzel, Jeff, Lynch, Henry, Garber, Judy, Easton, Douglas F., Peock, Susan, Cook, Margaret, Oliver, Clare T., Frost, Debra, Conroy, Don, Evans, D. Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Davidson, Rosemarie, Chu, Carol, Eccles, Diana, Selkirk, Christina G., Daly, Mary, Isaacs, Claudine, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Buecher, Bruno, Belotti, Muriel, Mazoyer, Sylvie, Barjhoux, Laure, Verny-Pierre, Carole, Lasset, Christine, Dreyfus, Hélène, Pujol, Pascal, Collonge-Rame, Marie-Agnès, Rookus, Matti A., Verhoef, Senno, Kriege, Mieke, Hoogerbrugge, Nicoline, Ausems, Margaret G. E. M., van Os, Theo A., Wijnen, Juul, Devilee, Peter, Meijers-Heijboer, Hanne E. J., Blok, Marinus J., Heikkinen, Tuomas, Nevanlinna, Heli, Jakubowska, Anna, Lubinski, Jan, Huzarski, Tomasz, Byrski, Tomasz, Durocher, Francine, Couch, Fergus J., Lindor, Noralene M., Wang, Xianshu, Thomassen, Mads, Domchek, Susan, Nathanson, Kate, Caligo, M. A., Jernstrom, Helena, Liljegren, Annelie, Ehrencrona, Hans, Karlsson, Per, Ganz, Patricia A., Olopade, Olufunmilayo I., Tomlinson, Gail, Neuhausen, Susan, Antoniou, Antonis C., Chenevix-Trench, Georgia and Rebbeck, Timothy R. (2011) Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers. Cancer Epidemiology, Biomarkers & Prevention, 20 (5), 1032-1038. (doi:10.1158/1055-9965.EPI-10-0909). (PMID:21393566)

Record type: Article

Abstract

BACKGROUND: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies.

METHODS: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated.

RESULTS: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk.

CONCLUSION: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers.

IMPACT: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.

This record has no associated files available for download.

More information

e-pub ahead of print date: 3 March 2011
Published date: May 2011
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352469
URI: http://eprints.soton.ac.uk/id/eprint/352469
PURE UUID: 5867f3d2-0900-47f2-aa92-102b9ab24c53
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 16 May 2013 09:27
Last modified: 15 Mar 2024 02:40

Export record

Altmetrics

Contributors

Author: Amanda B. Spurdle
Author: Louise Marquart
Author: Lesley McGuffog
Author: Sue Healey
Author: Olga Sinilnikova
Author: Fei Wan
Author: Xiaoqing Chen
Author: Jonathan Beesley
Author: Christian F. Singer
Author: Anne-Catharine Dressler
Author: Daphne Gschwantler-Kaulich
Author: Joanne L. Blum
Author: Nadine Tung
Author: Jeff Weitzel
Author: Henry Lynch
Author: Judy Garber
Author: Douglas F. Easton
Author: Susan Peock
Author: Margaret Cook
Author: Clare T. Oliver
Author: Debra Frost
Author: Don Conroy
Author: D. Gareth Evans
Author: Fiona Lalloo
Author: Ros Eeles
Author: Louise Izatt
Author: Rosemarie Davidson
Author: Carol Chu
Author: Diana Eccles ORCID iD
Author: Christina G. Selkirk
Author: Mary Daly
Author: Claudine Isaacs
Author: Dominique Stoppa-Lyonnet
Author: Olga M. Sinilnikova
Author: Bruno Buecher
Author: Muriel Belotti
Author: Sylvie Mazoyer
Author: Laure Barjhoux
Author: Carole Verny-Pierre
Author: Christine Lasset
Author: Hélène Dreyfus
Author: Pascal Pujol
Author: Marie-Agnès Collonge-Rame
Author: Matti A. Rookus
Author: Senno Verhoef
Author: Mieke Kriege
Author: Nicoline Hoogerbrugge
Author: Margaret G. E. M. Ausems
Author: Theo A. van Os
Author: Juul Wijnen
Author: Peter Devilee
Author: Hanne E. J. Meijers-Heijboer
Author: Marinus J. Blok
Author: Tuomas Heikkinen
Author: Heli Nevanlinna
Author: Anna Jakubowska
Author: Jan Lubinski
Author: Tomasz Huzarski
Author: Tomasz Byrski
Author: Francine Durocher
Author: Fergus J. Couch
Author: Noralene M. Lindor
Author: Xianshu Wang
Author: Mads Thomassen
Author: Susan Domchek
Author: Kate Nathanson
Author: M. A. Caligo
Author: Helena Jernstrom
Author: Annelie Liljegren
Author: Hans Ehrencrona
Author: Per Karlsson
Author: Patricia A. Ganz
Author: Olufunmilayo I. Olopade
Author: Gail Tomlinson
Author: Susan Neuhausen
Author: Antonis C. Antoniou
Author: Georgia Chenevix-Trench
Author: Timothy R. Rebbeck

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×