Gene-gene interactions in breast cancer susceptibility

Clare Turnbull; Sheila Seal; Anthony Renwick; Margaret Warren-Perry; Deborah Hughes; Anna Elliott; David Pernet; Susan Peock; Julian W. Adlard; Julian Barwell; Jonathan Berg; Angela F. Brady; Carole Brewer; Glen Brice; Cyril Chapman; Jackie Cook; Rosemarie Davidson; Alan Donaldson; Fiona Douglas; Lynn Greenhalgh; Alex Henderson; Louise Izatt; Ajith Kumar; Fiona Lalloo; Zosia Miedzybrodzka; Patrick J. Morrison; Joan Paterson; Mary Porteous; Mark T. Rogers; Susan Shanley; Lisa Walker; Munaza Ahmed; Diana Eccles; D. Gareth Evans; Peter Donnelly; Douglas F. Easton; Michael R. Stratton; Nazneen Rahman; EMBRACE, Breast Canc Susceptibility

doi:10.1093/hmg/ddr525

Gene-gene interactions in breast cancer susceptibility

Clare Turnbull
, Sheila Seal
, Anthony Renwick
, Margaret Warren-Perry
, Deborah Hughes
, Anna Elliott
, David Pernet
, Susan Peock
, Julian W. Adlard
, Julian Barwell
, Jonathan Berg
, Angela F. Brady
, Carole Brewer
, Glen Brice
, Cyril Chapman
, Jackie Cook
, Rosemarie Davidson
, Alan Donaldson
, Fiona Douglas
, Lynn Greenhalgh

Alex Henderson, Louise Izatt, Ajith Kumar, Fiona Lalloo, Zosia Miedzybrodzka, Patrick J. Morrison, Joan Paterson, Mary Porteous, Mark T. Rogers, Susan Shanley, Lisa Walker, Munaza Ahmed, Diana Eccles, D. Gareth Evans, Peter Donnelly, Douglas F. Easton, Michael R. Stratton, Nazneen Rahman, EMBRACE, Breast Canc Susceptibility

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

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 x 10(-4); ATM and BRCA1, P = 0.01; ATM and BRCA2, P = 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 x 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.

Original language	English
Pages (from-to)	958-962
Number of pages	5
Journal	Human Molecular Genetics
Volume	21
Issue number	4
DOIs	https://doi.org/10.1093/hmg/ddr525
Publication status	Published - 15 Feb 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

GENOME-WIDE ASSOCIATION
BRCA2 MUTATION CARRIERS
RISK
VARIANTS
ALLELES
LOCI
CHEK2-ASTERISK-1100DELC
PREDISPOSITION
POPULATION
CHEK2

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10.1093/hmg/ddr525

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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., ... EMBRACE, Breast Canc Susceptibility (2012). Gene-gene interactions in breast cancer susceptibility. Human Molecular Genetics, 21(4), 958-962. https://doi.org/10.1093/hmg/ddr525

@article{0e1ce083235c4936bab6c57254462427,

title = "Gene-gene interactions in breast cancer susceptibility",

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 x 10(-4); ATM and BRCA1, P = 0.01; ATM and BRCA2, P = 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 x 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.",

keywords = "GENOME-WIDE ASSOCIATION, BRCA2 MUTATION CARRIERS, RISK, VARIANTS, ALLELES, LOCI, CHEK2-ASTERISK-1100DELC, PREDISPOSITION, POPULATION, CHEK2",

author = "Clare Turnbull and Sheila Seal and Anthony Renwick and Margaret Warren-Perry and Deborah Hughes and Anna Elliott and David Pernet and Susan Peock and Adlard, \{Julian W.\} and Julian Barwell and Jonathan Berg and Brady, \{Angela F.\} and Carole Brewer and Glen Brice and Cyril Chapman and Jackie Cook and Rosemarie Davidson and Alan Donaldson and Fiona Douglas and Lynn Greenhalgh and Alex Henderson and Louise Izatt and Ajith Kumar and Fiona Lalloo and Zosia Miedzybrodzka and Morrison, \{Patrick J.\} and Joan Paterson and Mary Porteous and Rogers, \{Mark T.\} and Susan Shanley and Lisa Walker and Munaza Ahmed and Diana Eccles and Evans, \{D. Gareth\} and Peter Donnelly and Easton, \{Douglas F.\} and Stratton, \{Michael R.\} and Nazneen Rahman and \{EMBRACE, Breast Canc Susceptibility\}",

year = "2012",

month = feb,

day = "15",

doi = "10.1093/hmg/ddr525",

language = "English",

volume = "21",

pages = "958--962",

journal = "Human Molecular Genetics",

issn = "0964-6906",

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Turnbull, C, Seal, S, Renwick, A, Warren-Perry, M, Hughes, D, Elliott, A, Pernet, D, Peock, S, Adlard, JW, Barwell, J, Berg, J, Brady, AF, 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, PJ, Paterson, J, Porteous, M, Rogers, MT, Shanley, S, Walker, L, Ahmed, M, Eccles, D, Evans, DG, Donnelly, P, Easton, DF, Stratton, MR, Rahman, N & EMBRACE, Breast Canc Susceptibility 2012, 'Gene-gene interactions in breast cancer susceptibility', Human Molecular Genetics, vol. 21, no. 4, pp. 958-962. https://doi.org/10.1093/hmg/ddr525

TY - JOUR

T1 - Gene-gene interactions in breast cancer susceptibility

AU - Turnbull, Clare

AU - Seal, Sheila

AU - Renwick, Anthony

AU - Warren-Perry, Margaret

AU - Hughes, Deborah

AU - Elliott, Anna

AU - Pernet, David

AU - Peock, Susan

AU - Adlard, Julian W.

AU - Barwell, Julian

AU - Berg, Jonathan

AU - Brady, Angela F.

AU - Brewer, Carole

AU - Brice, Glen

AU - Chapman, Cyril

AU - Cook, Jackie

AU - Davidson, Rosemarie

AU - Donaldson, Alan

AU - Douglas, Fiona

AU - Greenhalgh, Lynn

AU - Henderson, Alex

AU - Izatt, Louise

AU - Kumar, Ajith

AU - Lalloo, Fiona

AU - Miedzybrodzka, Zosia

AU - Morrison, Patrick J.

AU - Paterson, Joan

AU - Porteous, Mary

AU - Rogers, Mark T.

AU - Shanley, Susan

AU - Walker, Lisa

AU - Ahmed, Munaza

AU - Eccles, Diana

AU - Evans, D. Gareth

AU - Donnelly, Peter

AU - Easton, Douglas F.

AU - Stratton, Michael R.

AU - Rahman, Nazneen

AU - EMBRACE, Breast Canc Susceptibility

PY - 2012/2/15

Y1 - 2012/2/15

N2 - 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 x 10(-4); ATM and BRCA1, P = 0.01; ATM and BRCA2, P = 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 x 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.

AB - 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 x 10(-4); ATM and BRCA1, P = 0.01; ATM and BRCA2, P = 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 x 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.

KW - GENOME-WIDE ASSOCIATION

KW - BRCA2 MUTATION CARRIERS

KW - RISK

KW - VARIANTS

KW - ALLELES

KW - LOCI

KW - CHEK2-ASTERISK-1100DELC

KW - PREDISPOSITION

KW - POPULATION

KW - CHEK2

U2 - 10.1093/hmg/ddr525

DO - 10.1093/hmg/ddr525

M3 - Article

C2 - 22072393

SN - 0964-6906

VL - 21

SP - 958

EP - 962

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 4

ER -

Gene-gene interactions in breast cancer susceptibility

Abstract

UN SDGs

Keywords

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