Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

Wang, Xianshu, Pankratz, V. Shane, Fredericksen, Zachary, Tarrell, Robert, Karaus, Mary, McGuffog, Lesley, Pharaoh, Paul D.P., Ponder, Bruce A.J., Dunning, Alison M., Peock, Susan, Cook, Margaret, Oliver, Clare, Frost, Debra, EMBRACE, Sinilnikova, Olga M., Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Houdayer, Claude, GEMO, Hogervorst, Frans B.L., Hooning, Maartje J., Ligtenberg, Marjolijn J., HEBON, Spurdle, Amanda, Chenevix-Trench, Georgia, kConFab, Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Domchek, Susan M., Nathanson, Katherine L., Rebbeck, Timothy R., Singer, Christian F., Gschwantler-Kaulich, Daphne, Dressler, Catherina, Fink, Anneliese, Szabo, Csilla I., Zikan, Michal, Foretova, Lenka, Claes, Kathleen, Thomas, Gilles, Hoover, Robert N., Hunter, David J., Chanock, Stephen J., Easton, Douglas F., Antoniou, Antonis C., Couch, Fergus J., Brown, Melissa, Cummings, Margaret and Lakhani, Sunil (2010) Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Human Molecular Genetics, 19 14: 2886-2897. doi:10.1093/hmg/ddq174

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Wang, Xianshu
Pankratz, V. Shane
Fredericksen, Zachary
Tarrell, Robert
Karaus, Mary
McGuffog, Lesley
Pharaoh, Paul D.P.
Ponder, Bruce A.J.
Dunning, Alison M.
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Sinilnikova, Olga M.
Stoppa-Lyonnet, Dominique
Mazoyer, Sylvie
Houdayer, Claude
Hogervorst, Frans B.L.
Hooning, Maartje J.
Ligtenberg, Marjolijn J.
Spurdle, Amanda
Chenevix-Trench, Georgia
Schmutzler, Rita K.
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy R.
Singer, Christian F.
Gschwantler-Kaulich, Daphne
Dressler, Catherina
Fink, Anneliese
Szabo, Csilla I.
Zikan, Michal
Foretova, Lenka
Claes, Kathleen
Thomas, Gilles
Hoover, Robert N.
Hunter, David J.
Chanock, Stephen J.
Easton, Douglas F.
Antoniou, Antonis C.
Couch, Fergus J.
Brown, Melissa
Cummings, Margaret
Lakhani, Sunil
Title Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2010-07-15
Sub-type Article (original research)
DOI 10.1093/hmg/ddq174
Volume 19
Issue 14
Start page 2886
End page 2897
Total pages 12
Place of publication Oxford, U.K.
Publisher Oxford University Press
Language eng
Formatted abstract
Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 × 3 10-3) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutationcarriersfromninecenters. Associations with breast cancer risk were assessed using Cox models weighted for penetrance. Eight SNPs in BRCA1 carriers and 12 SNPs in BRCA2 carriers, representing an enrichment over the number expected, were significantly associated with breast cancer risk (Ptrend < 0.01). The minor alleles of rs6138178 in SNRPB and rs6602595 in CAMK1D displayed the strongest associations in BRCA1 carriers (HR 5 0.78, 95% CI: 0.69-0.90, Ptrend = 3.6 × 10-4 and HR 5 1.25, 95% CI: 1.10-1.41, Ptrend = 4.2 × 10-4), whereas rs9393597 in LOC134997 and rs12652447 in FBXL7 showed the strongest associations in BRCA2 carriers (HR 5 1.55, 95% CI: 1.25-1.92, Ptrend 5 6 × 10-5 and HR 5 1.37, 95% CI: 1.16-1.62, Ptrend 5 1.7 × 10-4). The magnitude and direction of the associations were consistent with the original GWAS. In sub-sequent risk assessment studies, the loci appeared to interact multiplicatively for breast cancer risk in BRCA1 and BRCA2 carriers. Promising candidate SNPs from GWAS were identified as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. Upon further validation, these SNPs together with other genetic and environmental factors may improve breast cancer risk assessment in these populations.
© The Author 2010. Published by Oxford University Press. All rights reserved.
Keyword Estrogen-receptor
Confer susceptibility
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 41 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 01 Apr 2011, 00:00:16 EST by Debbie Banks on behalf of School of Medicine