Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-interacting genes

Timothy R. Rebbeck, Nandita Mitra, Susan M. Domchek, Fei Wan, Tara M. Friebel, Teo V. Tran, Christian F. Singer, Muy Kheng Maria Tea, Joanne L. Blum, Nadine Tung, Olufunmilayo I. Olopade, Jeffrey N. Weitzel, Henry T. Lynch, Carrie L. Snyder, Judy E. Garber, Antonis C. Antoniou, Susan Peock, D. Gareth Evans, Joan Paterson, M. John KennedyAlan Donaldson, Huw Dorkins, Douglas F. Easton, Wendy S. Rubinstein, Mary B. Daly, Claudine Isaacs, Heli Nevanlinna, Fergus J. Couch, Irene L. Andrulis, Eitan Freidman, Yael Laitman, Patricia A. Ganz, Gail E. Tomlinson, Susan L. Neuhausen, Steven A. Narod, Catherine M. Phelan, Roger Greenberg, Katherine L. Nathanson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Inherited BRCA1 mutations confer elevated cancer risk. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. A cohort of 2,825 BRCA1 mutation carriers was used to evaluate the association of haplotypes at ATM, BRCC36, BRCC45 (BRE), BRIP1 (BACH1/FANCJ), CTIP, ABRA1 (FAM175A), MERIT40, MRE11A, NBS1, PALB2 (FANCN), RAD50, RAD51, RAP80, and TOPBP1, and was associated with time to breast and ovarian cancer diagnosis. Statistically significant false discovery rate (FDR) adjusted P values for overall association of haplotypes (PFDR) with breast cancer were identified at ATM (PFDR = 0.029), BRCC45 (PFDR = 0.019), BRIP1 (PFDR = 0.008), CTIP (PFDR = 0.017), MERIT40 (PFDR = 0.019), NBS1 (PFDR = 0.003), RAD50 (PFDR = 0.014), and TOPBP1 (PFDR = 0.011). Haplotypes at ABRA1 (P FDR = 0.007), BRCC45 (PFDR = 0.016 and PFDR = 0.005 in two haplotype blocks), and RAP80 (PFDR <0.001) were associated with ovarian cancer risk. Overall, the data suggest that genomic variation at multiple loci that encode proteins that interact biologically with BRCA1 are associated with modified breast cancer and ovarian cancer risk in women who carry BRCA1 mutations.

Original languageEnglish (US)
Pages (from-to)5792-5805
Number of pages14
JournalCancer Research
Volume71
Issue number17
DOIs
StatePublished - Sep 1 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-interacting genes'. Together they form a unique fingerprint.

  • Cite this

    Rebbeck, T. R., Mitra, N., Domchek, S. M., Wan, F., Friebel, T. M., Tran, T. V., Singer, C. F., Tea, M. K. M., Blum, J. L., Tung, N., Olopade, O. I., Weitzel, J. N., Lynch, H. T., Snyder, C. L., Garber, J. E., Antoniou, A. C., Peock, S., Evans, D. G., Paterson, J., ... Nathanson, K. L. (2011). Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-interacting genes. Cancer Research, 71(17), 5792-5805. https://doi.org/10.1158/0008-5472.CAN-11-0773