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

Kristen N. Stevens, Xianshu Wang, Zachary Fredericksen, Vernon S. Pankratz, Mark H. Greene, Irene L. Andrulis, Mads Thomassen, Maria Caligo, 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 OffitMarion Piedmonte, Marco Montagna, Evgeny Imyanitov, Laima Tihomirova, Lara Sucheston, Mary Beattie, Susan L. Neuhausen, Csilla I. Szabo, Jacques Simard, Amanda B. Spurdle, Sue Healey, Xiaoqing Chen, Timothy R. Rebbeck, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Fergus J. Couch

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalBreast Cancer Research and Treatment
Volume136
Issue number1
DOIs
StatePublished - Nov 2012

Keywords

  • Association study
  • BRCA1
  • BRCA2
  • Genetic modifier

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers'. Together they form a unique fingerprint.

Cite this