Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Peterlongo, P.; Chang-Claude, J.; Moysich, 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.; 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.; Tibiletti, M. G.; Radice, P.; Vratimos, A.; Fostira, F.; Garber, J. E.; Donaldson, A.; Brewer, Carole; Foo, C.; Evans, D. G.; Frost, D.; Eccles, D.; Brady, A.; Cook, J.; Tischkowitz, M.; Adlard, J.; Barwell, J.; Walker, L.; Izatt, L.; Side, L. E.; Kennedy, M. J.; Rogers, M. T.; Porteous, M. E.; Morrison, P. J.; Platte, R.; Davidson, R.; Hodgson, S. V.; Ellis, S.; Cole, T.; 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.; Gemo Study Collaborators; Piedmonte, M.; Friedlander, M. L.; Rodriguez, G. C.; Copeland, L. J.; de la Hoya, M.; Segura, P. P.; Nevanlinna, H.; Aittomaki, K.; van Os, T. A.; Meijers-Heijboer, H. E.; van der Hout, A. H.; Vreeswijk, M. P.; Hoogerbrugge, N.; Ausems, M. G.; van Doorn, H. C.; Collee, J. M.; 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.; Kaulich, D. G.; Pfeiler, G.; Tea, M. K.; Phelan, C. M.; Greene, M. H.; Mai, P. L.; Rennert, G.; Mulligan, A. M.; Glendon, G.; Tchatchou, S.; Andrulis, I. L.; Toland, A. E.; Bojesen, A.; Pedersen, I. S.; Thomassen, M.; Jensen, U. B.; Laitman, Y.; Rantala, J.; von Wachenfeldt, A.; Ehrencrona, H.; Askmalm, M. S.; Borg, A.; Kuchenbaecker, K. B.; McGuffog, L.; Barrowdale, D.; Healey, S.; Lee, A.; Pharoah, P. D.; Chenevix-Trench, G.; K. ConFab Investigators; Antoniou, A. C.; Friedman, E.

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

URI

http://hdl.handle.net/11287/593942

Authors

Peterlongo, P.

Chang-Claude, J.

Moysich, K. B.

Rudolph, A.

Schmutzler, R. K.

Simard, J.

Soucy, P.

Eeles, R. A.

Easton, D. F.

Hamann, U.

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Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Type

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Publisher

Cancer Epidemiol Biomarkers Prev

DOI

10.1158/1055-9965.EPI-14-0532

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 in many 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 analysis was 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.

Citation

Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):308-16.

Publisher URL

http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25336561

Note

This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.

Collections

2015 RD&E publications
Genetics and genomics

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