The University of Southampton
University of Southampton Institutional Repository

Gene-gene interactions in breast cancer susceptibility

Gene-gene interactions in breast cancer susceptibility
Gene-gene interactions in breast cancer susceptibility
There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 × 10(-4); ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 × 10(-4); CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation.
958-962
Turnbull, C.
b24a936c-c216-44a3-83b8-1d1c54dfb1c6
Seal, S.
d2b5a329-b5eb-47dd-a8ef-7b9766eb541a
Renwick, A.
b940a6f2-8836-4bb7-a9f8-afaf2f8e12ba
Warren-Perry, M.
c785d2d2-e981-49a0-a7c8-9dd898ec9cab
Hughes, D.
f79fff93-6ce8-4530-b9eb-73ef0548970d
Elliott, A.
800fb06e-b744-43c4-bd14-0c251a877403
Pernet, D.
3e02ca2a-1504-4772-b310-0a47b89a06b4
Peock, S.
078d7af2-b419-40af-a52d-df59456d03b3
Adlard, J.W.
82ac4a46-41a1-4d60-a7c9-41a27843ef3e
Barwell, J.
696ff7d9-e20d-4004-bf1c-5682ee7f5f19
Berg, J.
2ba2b1b4-08a3-455b-b2b0-3c6f2d425f44
Brady, A.F.
97209414-001e-4cc7-acd7-5045d35650e3
Brewer, C.
f50e5721-93d3-43ef-8cd2-572f238d04be
Brice, G.
3198bea5-2124-4fc7-a4e9-285f6a50bb72
Chapman, C.
4d862e52-7459-4847-b2b4-6753386bdeec
Cook, J.
45c40993-978e-496e-9922-65774f13985e
Davidson, R.
9f684474-a989-4d8c-988c-a42e3d19db25
Donaldson, A.
ea10ac5a-4f77-4ef5-91d5-7f32ea33db36
Douglas, F.
9dc3db90-827e-419d-86f1-48e22b6845ab
Greenhalgh, L.
3e8784cb-64e7-461c-b4a1-9f1dcdebf216
Henderson, A.
ba6bffbb-5528-4869-b5f4-a8c142a47b6c
Izatt, L.
5cabcdef-374a-4441-b571-9c7b1665b720
Kumar, A.
d5d62c56-87f6-4ae1-ac67-2fb4bf8db422
Lalloo, F.
60a2edba-59dd-4e37-9b3d-9eff7f8f7106
Miedzybrodzka, Z.
88cf9144-bcf0-4490-a0e4-21d0df095155
Morrison, P.J.
cdcdba90-397b-4345-b409-7e2d1e1282d4
Paterson, J.
b6d85117-51f3-4ba4-b105-6c3c304a1805
Porteous, M.
cfcccad0-0a90-4ec6-ab3f-ec60eaf9de33
Rogers, M.T.
fbdb3c18-7bd3-42ae-8919-78433e498a11
Shanley, S.
8015c790-26c1-4697-8632-be90203bddde
Walker, L.
99ada328-aeda-4264-8fc8-3154e2090265
Ahmed, M.
b5631738-babc-42be-b182-d1ad111ef32f
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Evans, D.G.
b58c99fc-4da0-4d7e-b140-f22307befe5e
Donnelly, P.
a355b599-37af-46e9-81c4-7e394ec51b42
Easton, D.F.
ef4b7694-86fa-4568-969f-d0ee512127fc
Stratton, M.R.
e43300ce-fae0-4413-af97-185c3b34ec3d
Rahman, N.
6b59a4f8-b2c5-46a3-a660-66baab614029
Turnbull, C.
b24a936c-c216-44a3-83b8-1d1c54dfb1c6
Seal, S.
d2b5a329-b5eb-47dd-a8ef-7b9766eb541a
Renwick, A.
b940a6f2-8836-4bb7-a9f8-afaf2f8e12ba
Warren-Perry, M.
c785d2d2-e981-49a0-a7c8-9dd898ec9cab
Hughes, D.
f79fff93-6ce8-4530-b9eb-73ef0548970d
Elliott, A.
800fb06e-b744-43c4-bd14-0c251a877403
Pernet, D.
3e02ca2a-1504-4772-b310-0a47b89a06b4
Peock, S.
078d7af2-b419-40af-a52d-df59456d03b3
Adlard, J.W.
82ac4a46-41a1-4d60-a7c9-41a27843ef3e
Barwell, J.
696ff7d9-e20d-4004-bf1c-5682ee7f5f19
Berg, J.
2ba2b1b4-08a3-455b-b2b0-3c6f2d425f44
Brady, A.F.
97209414-001e-4cc7-acd7-5045d35650e3
Brewer, C.
f50e5721-93d3-43ef-8cd2-572f238d04be
Brice, G.
3198bea5-2124-4fc7-a4e9-285f6a50bb72
Chapman, C.
4d862e52-7459-4847-b2b4-6753386bdeec
Cook, J.
45c40993-978e-496e-9922-65774f13985e
Davidson, R.
9f684474-a989-4d8c-988c-a42e3d19db25
Donaldson, A.
ea10ac5a-4f77-4ef5-91d5-7f32ea33db36
Douglas, F.
9dc3db90-827e-419d-86f1-48e22b6845ab
Greenhalgh, L.
3e8784cb-64e7-461c-b4a1-9f1dcdebf216
Henderson, A.
ba6bffbb-5528-4869-b5f4-a8c142a47b6c
Izatt, L.
5cabcdef-374a-4441-b571-9c7b1665b720
Kumar, A.
d5d62c56-87f6-4ae1-ac67-2fb4bf8db422
Lalloo, F.
60a2edba-59dd-4e37-9b3d-9eff7f8f7106
Miedzybrodzka, Z.
88cf9144-bcf0-4490-a0e4-21d0df095155
Morrison, P.J.
cdcdba90-397b-4345-b409-7e2d1e1282d4
Paterson, J.
b6d85117-51f3-4ba4-b105-6c3c304a1805
Porteous, M.
cfcccad0-0a90-4ec6-ab3f-ec60eaf9de33
Rogers, M.T.
fbdb3c18-7bd3-42ae-8919-78433e498a11
Shanley, S.
8015c790-26c1-4697-8632-be90203bddde
Walker, L.
99ada328-aeda-4264-8fc8-3154e2090265
Ahmed, M.
b5631738-babc-42be-b182-d1ad111ef32f
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Evans, D.G.
b58c99fc-4da0-4d7e-b140-f22307befe5e
Donnelly, P.
a355b599-37af-46e9-81c4-7e394ec51b42
Easton, D.F.
ef4b7694-86fa-4568-969f-d0ee512127fc
Stratton, M.R.
e43300ce-fae0-4413-af97-185c3b34ec3d
Rahman, N.
6b59a4f8-b2c5-46a3-a660-66baab614029

Turnbull, C., Seal, S., Renwick, A., Warren-Perry, M., Hughes, D., Elliott, A., Pernet, D., Peock, S., Adlard, J.W., Barwell, J., Berg, J., Brady, A.F., Brewer, C., Brice, G., Chapman, C., Cook, J., Davidson, R., Donaldson, A., Douglas, F., Greenhalgh, L., Henderson, A., Izatt, L., Kumar, A., Lalloo, F., Miedzybrodzka, Z., Morrison, P.J., Paterson, J., Porteous, M., Rogers, M.T., Shanley, S., Walker, L., Ahmed, M., Eccles, D., Evans, D.G., Donnelly, P., Easton, D.F., Stratton, M.R. and Rahman, N. (2012) Gene-gene interactions in breast cancer susceptibility. Human Molecular Genetics, 21 (4), 958-962. (doi:10.1093/hmg/ddr525). (PMID:22072393)

Record type: Article

Abstract

There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 × 10(-4); ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 × 10(-4); CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation.

Full text not available from this repository.

More information

Published date: 15 February 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352341
URI: https://eprints.soton.ac.uk/id/eprint/352341
PURE UUID: 4d79f394-5de0-4d66-93bf-451c3a468801

Catalogue record

Date deposited: 13 May 2013 10:27
Last modified: 16 Jul 2019 21:34

Export record

Altmetrics

Contributors

Author: C. Turnbull
Author: S. Seal
Author: A. Renwick
Author: M. Warren-Perry
Author: D. Hughes
Author: A. Elliott
Author: D. Pernet
Author: S. Peock
Author: J.W. Adlard
Author: J. Barwell
Author: J. Berg
Author: A.F. Brady
Author: C. Brewer
Author: G. Brice
Author: C. Chapman
Author: J. Cook
Author: R. Davidson
Author: A. Donaldson
Author: F. Douglas
Author: L. Greenhalgh
Author: A. Henderson
Author: L. Izatt
Author: A. Kumar
Author: F. Lalloo
Author: Z. Miedzybrodzka
Author: P.J. Morrison
Author: J. Paterson
Author: M. Porteous
Author: M.T. Rogers
Author: S. Shanley
Author: L. Walker
Author: M. Ahmed
Author: D. Eccles
Author: D.G. Evans
Author: P. Donnelly
Author: D.F. Easton
Author: M.R. Stratton
Author: N. Rahman

University divisions

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 https://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.

×