Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
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Authors
Peterlongo, P
Chang-Claude, J
Moysich, KB
Rudolph, A
Schmutzler, RK
Simard, J
Soucy, P
Eeles, RA
Easton, DF
Hamann, U
Wilkening, S
Chen, B
Rookus, MA
Schmidt, MK
van der Baan, FH
Spurdle, AB
Walker, LC
Lose, F
Maia, A-T
Montagna, M
Matricardi, L
Lubinski, J
Jakubowska, A
Gómez Garcia, EB
Olopade, OI
Nussbaum, RL
Nathanson, KL
Domchek, SM
Rebbeck, TR
Arun, BK
Karlan, BY
Orsulic, S
Lester, J
Chung, WK
Miron, A
Southey, MC
Goldgar, DE
Buys, SS
Janavicius, R
Dorfling, CM
van Rensburg, EJ
Ding, YC
Neuhausen, SL
Hansen, TVO
Gerdes, A-M
Ejlertsen, B
Jønson, L
Osorio, A
Martínez-Bouzas, C
Benitez, J
Conway, EE
Blazer, KR
Weitzel, JN
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, MG
Radice, P
Vratimos, A
Fostira, F
Garber, JE
Donaldson, A
Brewer, C
Foo, C
Evans, DGR
Frost, D
Eccles, D
Brady, A
Cook, J
Tischkowitz, M
Adlard, J
Barwell, J
Walker, L
Izatt, L
Side, LE
Kennedy, MJ
Rogers, MT
Porteous, ME
Morrison, PJ
Platte, R
Davidson, R
Hodgson, SV
Ellis, S
Cole, T
EMBRACE,
Godwin, AK
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, OM
Caron, O
Pujol, P
Mazoyer, S
Belotti, M
GEMO Study Collaborators,
Piedmonte, M
Friedlander, ML
Rodriguez, GC
Copeland, LJ
de la Hoya, M
Segura, PP
Nevanlinna, H
Aittomäki, K
van Os, TAM
Meijers-Heijboer, HEJ
van der Hout, AH
Vreeswijk, MPG
Hoogerbrugge, N
Ausems, MGEM
van Doorn, HC
Collée, JM
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, MR
Olswold, C
Couch, FJ
Lindor, NM
Wang, X
Szabo, CI
Offit, K
Corines, M
Jacobs, L
Robson, ME
Zhang, L
Joseph, V
Berger, A
Singer, CF
Rappaport, C
Kaulich, DG
Pfeiler, G
Tea, M-KM
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Mulligan, AM
Glendon, G
Tchatchou, S
Andrulis, IL
Toland, AE
Bojesen, A
Pedersen, IS
Thomassen, M
Jensen, UB
Laitman, Y
Rantala, J
von Wachenfeldt, A
Ehrencrona, H
Askmalm, MS
Borg, Å
Kuchenbaecker, KB
McGuffog, L
Barrowdale, D
Healey, S
Lee, A
Pharoah, PDP
Chenevix-Trench, G
KConFab Investigators,
Antoniou, AC
Friedman, E
Chang-Claude, J
Moysich, KB
Rudolph, A
Schmutzler, RK
Simard, J
Soucy, P
Eeles, RA
Easton, DF
Hamann, U
Wilkening, S
Chen, B
Rookus, MA
Schmidt, MK
van der Baan, FH
Spurdle, AB
Walker, LC
Lose, F
Maia, A-T
Montagna, M
Matricardi, L
Lubinski, J
Jakubowska, A
Gómez Garcia, EB
Olopade, OI
Nussbaum, RL
Nathanson, KL
Domchek, SM
Rebbeck, TR
Arun, BK
Karlan, BY
Orsulic, S
Lester, J
Chung, WK
Miron, A
Southey, MC
Goldgar, DE
Buys, SS
Janavicius, R
Dorfling, CM
van Rensburg, EJ
Ding, YC
Neuhausen, SL
Hansen, TVO
Gerdes, A-M
Ejlertsen, B
Jønson, L
Osorio, A
Martínez-Bouzas, C
Benitez, J
Conway, EE
Blazer, KR
Weitzel, JN
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, MG
Radice, P
Vratimos, A
Fostira, F
Garber, JE
Donaldson, A
Brewer, C
Foo, C
Evans, DGR
Frost, D
Eccles, D
Brady, A
Cook, J
Tischkowitz, M
Adlard, J
Barwell, J
Walker, L
Izatt, L
Side, LE
Kennedy, MJ
Rogers, MT
Porteous, ME
Morrison, PJ
Platte, R
Davidson, R
Hodgson, SV
Ellis, S
Cole, T
EMBRACE,
Godwin, AK
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, OM
Caron, O
Pujol, P
Mazoyer, S
Belotti, M
GEMO Study Collaborators,
Piedmonte, M
Friedlander, ML
Rodriguez, GC
Copeland, LJ
de la Hoya, M
Segura, PP
Nevanlinna, H
Aittomäki, K
van Os, TAM
Meijers-Heijboer, HEJ
van der Hout, AH
Vreeswijk, MPG
Hoogerbrugge, N
Ausems, MGEM
van Doorn, HC
Collée, JM
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, MR
Olswold, C
Couch, FJ
Lindor, NM
Wang, X
Szabo, CI
Offit, K
Corines, M
Jacobs, L
Robson, ME
Zhang, L
Joseph, V
Berger, A
Singer, CF
Rappaport, C
Kaulich, DG
Pfeiler, G
Tea, M-KM
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Mulligan, AM
Glendon, G
Tchatchou, S
Andrulis, IL
Toland, AE
Bojesen, A
Pedersen, IS
Thomassen, M
Jensen, UB
Laitman, Y
Rantala, J
von Wachenfeldt, A
Ehrencrona, H
Askmalm, MS
Borg, Å
Kuchenbaecker, KB
McGuffog, L
Barrowdale, D
Healey, S
Lee, A
Pharoah, PDP
Chenevix-Trench, G
KConFab Investigators,
Antoniou, AC
Friedman, E
Document Type
Journal Article
Date
2015-01-01
Date Accepted
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 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 epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015, 24 (1), pp. 308 - 316
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1055-9965
eISSN
1538-7755
Research Team
Oncogenetics