Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-11

AUTHORS

Kristen N. Stevens, Xianshu Wang, Zachary Fredericksen, Vernon S. Pankratz, Mark H. Greene, Irene L. Andrulis, Mads Thomassen, Maria Caligo, Swedish Breast Cancer Study, Sweden (SWE-BRCA), Katherine L. Nathanson, Anna Jakubowska, Ana Osorio, Ute Hamann, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Melissa Southey, Saundra S. Buys, Christian F. Singer, Thomas V. O. Hansen, Adalgeir Arason, Kenneth Offit, Marion Piedmonte, Marco Montagna, Evgeny Imyanitov, Laima Tihomirova, Lara Sucheston, Mary Beattie, HEreditary Breast and Ovarian Cancer Group Netherlands (HEBON), German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), Susan L. Neuhausen, CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT Team), Csilla I. Szabo, kConFab, Jacques Simard, Amanda B. Spurdle, Sue Healey, Xiaoqing Chen, Timothy R. Rebbeck, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Fergus J. Couch

ABSTRACT

Several common germline variants identified through genome-wide association studies of breast cancer risk in the general population have recently been shown to be associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. When combined, these variants can identify marked differences in the absolute risk of developing breast cancer for mutation carriers, suggesting that additional modifier loci may further enhance individual risk assessment for BRCA1 and BRCA2 mutation carriers. Recently, a common variant on 6p22 (rs9393597) was found to be associated with increased breast cancer risk for BRCA2 mutation carriers [hazard ratio (HR) = 1.55, 95 % confidence interval (CI) 1.25-1.92, p = 6.0 × 10(-5)]. This observation was based on data from GWAS studies in which, despite statistical correction for multiple comparisons, the possibility of false discovery remains a concern. Here, we report on an analysis of this variant in an additional 6,165 BRCA1 and 3,900 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). In this replication analysis, rs9393597 was not associated with breast cancer risk for BRCA2 mutation carriers (HR = 1.09, 95 % CI 0.96-1.24, p = 0.18). No association with ovarian cancer risk for BRCA1 or BRCA2 mutation carriers or with breast cancer risk for BRCA1 mutation carriers was observed. This follow-up study suggests that, contrary to our initial report, this variant is not associated with breast cancer risk among individuals with germline BRCA2 mutations. More... »

PAGES

295-302

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-012-2255-6

DOI

http://dx.doi.org/10.1007/s10549-012-2255-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047048576

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23011509


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