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.
Original language | English |
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Pages (from-to) | 1032-1038 |
Number of pages | 7 |
Journal | Cancer Epidemiology Biomarkers and Prevention |
Volume | 20 |
Issue number | 5 |
DOIs | |
State | Published - May 2011 |
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All Science Journal Classification (ASJC) codes
- Epidemiology
- Oncology
Cite this
Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers. / 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 T.; 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, Margreet 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; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Durocher, Francine; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Thomassen, Mads; Domchek, Susan; Nathanson, Kate; Caligo, M. A.; Jernström, Helena; Liljegren, Annelie; Ehrencrona, Hans; Karlsson, Per; Ganz, Patricia A.; Olopade, Olufunmilayo I.; Tomlinson, Gail; Neuhausen, Susan; Antoniou, Antonis C.; Chenevix-Trench, Georgia; Rebbeck, Timothy R.
In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 5, 05.2011, p. 1032-1038.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common genetic variation at BARD1 is not associated with breast cancer risk in BRCA1 or BRCA2 mutation carriers
AU - Spurdle, Amanda B.
AU - Marquart, Louise
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Sinilnikova, Olga
AU - Wan, Fei
AU - Chen, Xiaoqing
AU - Beesley, Jonathan
AU - Singer, Christian F.
AU - Dressler, Anne Catharine
AU - Gschwantler-Kaulich, Daphne
AU - Blum, Joanne L.
AU - Tung, Nadine
AU - Weitzel, Jeff
AU - Lynch, Henry T.
AU - Garber, Judy
AU - Easton, Douglas F.
AU - Peock, Susan
AU - Cook, Margaret
AU - Oliver, Clare T.
AU - Frost, Debra
AU - Conroy, Don
AU - Evans, D. Gareth
AU - Lalloo, Fiona
AU - Eeles, Ros
AU - Izatt, Louise
AU - Davidson, Rosemarie
AU - Chu, Carol
AU - Eccles, Diana
AU - Selkirk, Christina G.
AU - Daly, Mary
AU - Isaacs, Claudine
AU - Stoppa-Lyonnet, Dominique
AU - Sinilnikova, Olga M.
AU - Buecher, Bruno
AU - Belotti, Muriel
AU - Mazoyer, Sylvie
AU - Barjhoux, Laure
AU - Verny-Pierre, Carole
AU - Lasset, Christine
AU - Dreyfus, Hélène
AU - Pujol, Pascal
AU - Collonge-Rame, Marie Agnès
AU - Rookus, Matti A.
AU - Verhoef, Senno
AU - Kriege, Mieke
AU - Hoogerbrugge, Nicoline
AU - Ausems, Margreet G E M
AU - Van Os, Theo A.
AU - Wijnen, Juul
AU - Devilee, Peter
AU - Meijers-Heijboer, Hanne E J
AU - Blok, Marinus J.
AU - Heikkinen, Tuomas
AU - Nevanlinna, Heli
AU - Jakubowska, Anna
AU - Lubiński, Jan
AU - Huzarski, Tomasz
AU - Byrski, Tomasz
AU - Durocher, Francine
AU - Couch, Fergus J.
AU - Lindor, Noralane M.
AU - Wang, Xianshu
AU - Thomassen, Mads
AU - Domchek, Susan
AU - Nathanson, Kate
AU - Caligo, M. A.
AU - Jernström, Helena
AU - Liljegren, Annelie
AU - Ehrencrona, Hans
AU - Karlsson, Per
AU - Ganz, Patricia A.
AU - Olopade, Olufunmilayo I.
AU - Tomlinson, Gail
AU - Neuhausen, Susan
AU - Antoniou, Antonis C.
AU - Chenevix-Trench, Georgia
AU - Rebbeck, Timothy R.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79955775590&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955775590&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-10-0909
DO - 10.1158/1055-9965.EPI-10-0909
M3 - Article
C2 - 21393566
AN - SCOPUS:79955775590
VL - 20
SP - 1032
EP - 1038
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 5
ER -