Modification of BRCA1-Associated Breast and Ovarian Cancer Risk by BRCA1-Interacting Genes
| Autor: | Katherine L. Nathanson, Fergus J. Couch, Patricia A. Ganz, Olufunmilayo I. Olopade, Susan Peock, D. Gareth Evans, Susan L. Neuhausen, Douglas F. Easton, Wendy S. Rubinstein, Roger A. Greenberg, Muy Kheng Tea, Heli Nevanlinna, Nadine Tung, Jeffrey N. Weitzel, Steven A. Narod, Judy Garber, Nandita Mitra, Mary B. Daly, Antonis C. Antoniou, Joan Paterson, Teo V. Tran, Catherine M. Phelan, Henry T. Lynch, Yael Laitman, Christian F. Singer, Eitan Freidman, Claudine Isaacs, Huw Dorkins, Fei Wan, Carrie Snyder, Alan Donaldson, Gail E. Tomlinson, Joanne L. Blum, Timothy R. Rebbeck, Susan M. Domchek, Irene L. Andrulis, M. John Kennedy, Tara M. Friebel |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Risk Cancer Research PALB2 Single-nucleotide polymorphism Breast Neoplasms Biology Article Cohort Studies 03 medical and health sciences Young Adult 0302 clinical medicine Breast cancer BARD1 medicine Humans skin and connective tissue diseases 030304 developmental biology Aged Genetics Aged 80 and over Ovarian Neoplasms 0303 health sciences BRCA1 Protein Haplotype BRIP1 Cancer Genetic Variation Middle Aged medicine.disease 3. Good health MRE11A Oncology Genetic Loci 030220 oncology & carcinogenesis Mutation Female |
| Zdroj: | Cancer research. 71(17) |
| ISSN: | 1538-7445 |
| Popis: | 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 (PFDR = 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. Cancer Res; 71(17); 5792–805. ©2011 AACR. |
| Databáze: | OpenAIRE |
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