| Authors: |
Peterlongo, P.; Chang-Claude, J.; Boysich, K. B.; Rudolph, A.; Schmutzler, R. K.; Simard, J.; Soucy, P.; Eeles, R. A.; Easton, D. F.; Hamann, U.; Wilkening, S.; Chen, B.; Rookus, M. A.; Schmidt, M. K.; van der Baan, F. H.; Spurdle, A. B.; Walker, L. C.; Lose, F.; Maia, A. T.; Montagna, M.; Matricardi, L.; Lubinski, J.; Jakubowska, A.; Gomez Garcia, E. B.; Olopade, O. I.; Nussbaum, R. L.; Nathanson, K. L.; Domchek, S. M.; Rebbeck, T. R.; Arun, B. K.; Karlan, B. Y.; Orsulic, S.; Lester, J.; Chung, W. K.; Miron, A.; Southey, M. C.; Goldgar, D. E.; Buys, S. S.; Janavicius, R.; Dorfling, C. M.; van Rensburg, E. J.; Ding, Y. C.; Neuhausen, S. L.; Hansen, T. V. O.; Gerdes, A. M.; Ejlertsen, B.; Jonson, L.; Osorio, A.; Martinez-Bouzas, C.; Benitez, J.; Conway, E. E.; Blazer, K. R.; Weitzel, J. N.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Barile, M.; Ficarazzi, F.; Mariette, F.; Fortuzzi, S.; Viel, A.; Giannini, G.; Papi, L.; Martayan, A.; Grazia Tibiletti, M.; Radice, P.; Vratimos, A.; Fostira, F.; Garber, J. E.; Donaldson, A.; Brewer, C.; Foo, C.; Evans, D. G. R.; Frost, D.; Eccles, D.; Brady, A.; Cook, J.; Tischkowitz, M.; Adlard, J.; Barwell, J.; Walker, L.; Izatt, L.; Side, L. E.; Kennedy, M. J.; Roger, M. T.; Porteous, M. E.; Morrison, P. J.; Platte, R.; Davidson, R.; Hodgson, S. V.; Ellis, S.; Cole, T.; on behalf of EMBRACE; Godwin, A. K.; Claes, K.; Van Maerken, T.; Meindl, A.; Gehrig, A.; Sutter, C.; Engel, C.; Niederacher, D.; Steinemann, D.; Plendl, H.; Kast, K.; Rhiem, K.; Ditsch, N.; Arnold, N.; Varon-Mateeva, R.; Wappenschmidt, B.; Wang-Gohrke, S.; Bressac-de Paillerets, B.; Buecher, B.; Delnatte, c.; Houdayer, C.; Stoppa-Lyonnet, D.; Damiola, F.; Coupier, I.; Barjhoux, L.; Venat-Bouvet, L.; Golmard, L.; Boutry-Kryza, N.; Sinilnikova, O. M.; Caron, O.; Pujol, P.; Mazoyer, S.; Belotti, M.; on behalf of GEMO Study Collaborators; Piedmonte, M.; Friedlander, M. L.; Rodriguez, G. C.; Copeland, L. J.; de la Hoya, M.; Perez Segura, P.; Nevanlinna, H.; Aittomaki, K.; van Os, T. A. M.; Meijer-Heijboer, H. E. J.; van der Hout, A. H.; Vreeswijk, M. P. G.; Hoogerbrugge, N.; Ausems, M. G. E. M.; van Doorn, H. C.; Collee, J. M.; on behalf of HEBON; Olah, E.; Diez, O.; Blanco, I.; Lazaro, C.; Brunet, J.; Feliubadalo, L.; Cybulski, C.; Gronwald, J.; Durda, K.; Jaworska-Bieniek, K.; Sukiennicki, G.; Arason, A.; Chiquette, J.; Teixeira, M. R.; Olswold, C.; Couch, F. J.; Lindor, N. M.; Wang, X.; Szabo, C. I.; Offit, K.; Corines, M.; Jacobs, L.; Robson, M. E.; Zhang, L.; Joseph, V.; Berger, A.; Singer, C. F.; Rappaport, C.; Geschwantler Kaulich, D.; Pfeiler, G.; Tea, M. K. M.; Phelan, C. M.; Greene, M. H.; Mai, P. L.; Rennert, G.; Mulligan, A. M.; Glendon, G.; Tchatchou, S.; Andrulis, I. L.; Ewart Toland, A.; Bojesen, A.; Sokilde Pedersen, I.; Thomassen, M.; Jensen, U. B.; Laitman, Y.; Rantala, J.; von Wachenfeldt, A.; Ehrencrona, H.; Stenmark Askmalm, M.; Borg, A.; Kuchenbaecker, K. B.; McGuffog, L.; Barrowdale, D.; Healey, S.; Lee, A.; Pharoah, P. D. P.; Chenevix-Trench, G.; on behalf of KConFab Investigators; Antoniou, A. C.; Friedman, E. |
| Article Title: |
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers |
| Abstract: |
Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants inmany candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysiswas performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. |
| Keywords: |
adult; gene mutation; cancer risk; ovary cancer; breast cancer; genetic association; genetic variability; genotype; oncogene; tumor suppressor gene; gene location; penetrance; human; female; priority journal; article
|
| Journal Title: |
Cancer Epidemiology Biomarkers and Prevention
|
| Volume: |
24 |
| Issue: |
1 |
| ISSN: |
1055-9965 |
| Publisher: |
American Association for Cancer Research
|
| Date Published: |
2015-01-01 |
| Start Page: |
308 |
| End Page: |
316 |
| Language: |
English |
| DOI: |
10.1158/1055-9965.epi-14-0532
|
| PROVIDER: |
scopus
|
| PUBMED: |
25336561
|
| PMCID: |
PMC4294951
|
| DOI/URL: |
|
| Notes: |
Export Date: 2 February 2015 -- Source: Scopus |
