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

P Peterlongo; J Chang-Claude; K B Moysich; A Rudolph; R K Schmutzler; J Simard; P Soucy; R A Eeles; D F Easton; U Hamann; S Wilkening; B Chen; M A Rookus; M K Schmidt; F H Van Der Baan; A B Spurdle; L C Walker; Felicity Lose; A T Maia; M Montagna; L Matricardi; J Lubinski; A Jakubowska; E B G Garcia; O I Olopade; R L Nussbaum; K L Nathanson; S M Domchek; T R Rebbeck; B K Arun; B Y Karlan; S Orsulic; J Lester; W K Chung; A Miron; M C Southey; D E Goldgar; S S Buys; R Janavicius; C M Dorfling; E J Van Rensburg; Y C Ding; S L Neuhausen; T V O Hansen; A M Gerdes; B Ejlertsen; L Jønson; A Osorio; C Martínez-Bouzas; J Benitez; E E Conway; K R Blazer; J N Weitzel; S Manoukian; B Peissel; D Zaffaroni; G Scuvera; M Barile; F Ficarazzi; F Mariette; S Fortuzzi; A Viel; G Giannini; L Papi; A Martayan; M G Tibiletti; P Radice; A Vratimos; F Fostira; J E Garber; A Donaldson; C Brewer; C Foo; D G R Evans; Debra Frost; D Eccles; A Brady; J Cook; J Barwell; M Tischkowitz; L Walker; J Adlard; L Izatt; L E Side; M J Kennedy; M T Rogers; M E Porteous; P J Morrison; R Platte; R Davidson; S V Hodgson; S Ellis; T Cole; A K Godwin; K Claes; T Van Maerken; A Meindl; A Gehrig; C Sutter; C Engel; D Niederacher; D Steinemann; H Plendl; K Kast; K Rhiem; N Ditsch; N Arnold; R Varon-Mateeva; B Wappenschmidt; S Wang-Gohrke; B Bressac-De Paillerets; B Buecher; C Delnatte; C Houdayer; D Stoppa-Lyonnet; F Damiola; I Coupier; L Barjhoux; L Venat-Bouvet; L Golmard; N Boutry-Kryza; O M Sinilnikova; O Caron; P Pujol; S Mazoyer; M Belotti; M Piedmonte; M L Friedlander; G C Rodriguez; L J Copeland; M De La Hoya; P P Segura; H Nevanlinna; K Aittomäki; T A M Van Os; H E J Meijers-Heijboer; A H Van Der Hout; M P G Vreeswijk; N Hoogerbrugge; M G E M Ausems; H C Van Doorn; J M Collee; E Olah; O Diez; I Blanco; C Lazaro; J Brunet; L Feliubadalo; C Cybulski; J Gronwald; K Durda; K Jaworska-Bieniek; G Sukiennicki; A Arason; J Chiquette; M R Teixeira; C Olswold; F J Couch; N M Lindor; X Wang; C I Szabo; K Offit; M Corines; L Jacobs; M E Robson; L Zhang; V Joseph; A Berger; C F Singer; C Rappaport; D G Kaulich; G Pfeiler; M K M Tea; C M Phelan; M H Greene; P L Mai; G Rennert; A M Mulligan; G Glendon; S Tchatchou; I L Andrulis; A E Toland; A Bojesen; I S Pedersen; M Thomassen; U B Jensen; Y Laitman; J Rantala; A Von Wachenfeldt; H Ehrencrona; M S Askmalm; A Borg; K B Kuchenbaecker; L McGuffog; D Barrowdale; S Healey; A Lee; P D P Pharoah; G Chenevix-Trench; A C Antoniou; E Friedman

doi:10.1158/1055-9965.EPI-14-0532

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

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

P Peterlongo, J Chang-Claude, K B Moysich, A Rudolph, R K Schmutzler, J Simard, P Soucy, R A Eeles, D F Easton, U Hamann, …

Cancer Epidemiology Biomarkers and Prevention, Vol.24(1), pp.308-316

2015

DOI: https://doi.org/10.1158/1055-9965.EPI-14-0532

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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. © 2014 American Association for Cancer Research.

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Title: Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
Authors: P Peterlongo (Author)
J Chang-Claude (Author)
K B Moysich (Author)
A Rudolph (Author)
R K Schmutzler (Author)
J Simard (Author)
P Soucy (Author)
R A Eeles (Author)
D F Easton (Author)
U Hamann (Author)
S Wilkening (Author)
B Chen (Author)
M A Rookus (Author)
M K Schmidt (Author)
F H Van Der Baan (Author)
A B Spurdle (Author)
L C Walker (Author)
Felicity Lose (Author) - Queensland Institute of Medical Research
A T Maia (Author)
M Montagna (Author)
L Matricardi (Author)
J Lubinski (Author)
A Jakubowska (Author)
E B G Garcia (Author)
O I Olopade (Author)
R L Nussbaum (Author)
K L Nathanson (Author)
S M Domchek (Author)
T R Rebbeck (Author)
B K Arun (Author)
B Y Karlan (Author)
S Orsulic (Author)
J Lester (Author)
W K Chung (Author)
A Miron (Author)
M C Southey (Author)
D E Goldgar (Author)
S S Buys (Author)
R Janavicius (Author)
C M Dorfling (Author)
E J Van Rensburg (Author)
Y C Ding (Author)
S L Neuhausen (Author)
T V O Hansen (Author)
A M Gerdes (Author)
B Ejlertsen (Author)
L Jønson (Author)
A Osorio (Author)
C Martínez-Bouzas (Author)
J Benitez (Author)
E E Conway (Author)
K R Blazer (Author)
J N Weitzel (Author)
S Manoukian (Author)
B Peissel (Author)
D Zaffaroni (Author)
G Scuvera (Author)
M Barile (Author)
F Ficarazzi (Author)
F Mariette (Author)
S Fortuzzi (Author)
A Viel (Author)
G Giannini (Author)
L Papi (Author)
A Martayan (Author)
M G Tibiletti (Author)
P Radice (Author)
A Vratimos (Author)
F Fostira (Author)
J E Garber (Author)
A Donaldson (Author)
C Brewer (Author)
C Foo (Author)
D G R Evans (Author)
Debra Frost (Author)
D Eccles (Author)
A Brady (Author)
J Cook (Author)
J Barwell (Author)
M Tischkowitz (Author)
L Walker (Author)
J Adlard (Author)
L Izatt (Author)
L E Side (Author)
M J Kennedy (Author)
M T Rogers (Author)
M E Porteous (Author)
P J Morrison (Author)
R Platte (Author)
R Davidson (Author)
S V Hodgson (Author)
S Ellis (Author)
T Cole (Author)
A K Godwin (Author)
K Claes (Author)
T Van Maerken (Author)
A Meindl (Author)
A Gehrig (Author)
C Sutter (Author)
C Engel (Author)
D Niederacher (Author)
D Steinemann (Author)
H Plendl (Author)
K Kast (Author)
K Rhiem (Author)
N Ditsch (Author)
N Arnold (Author)
R Varon-Mateeva (Author)
B Wappenschmidt (Author)
S Wang-Gohrke (Author)
B Bressac-De Paillerets (Author)
B Buecher (Author)
C Delnatte (Author)
C Houdayer (Author)
D Stoppa-Lyonnet (Author)
F Damiola (Author)
I Coupier (Author)
L Barjhoux (Author)
L Venat-Bouvet (Author)
L Golmard (Author)
N Boutry-Kryza (Author)
O M Sinilnikova (Author)
O Caron (Author)
P Pujol (Author)
S Mazoyer (Author)
M Belotti (Author)
M Piedmonte (Author)
M L Friedlander (Author)
G C Rodriguez (Author)
L J Copeland (Author)
M De La Hoya (Author)
P P Segura (Author)
H Nevanlinna (Author)
K Aittomäki (Author)
T A M Van Os (Author)
H E J Meijers-Heijboer (Author)
A H Van Der Hout (Author)
M P G Vreeswijk (Author)
N Hoogerbrugge (Author)
M G E M Ausems (Author)
H C Van Doorn (Author)
J M Collee (Author)
E Olah (Author)
O Diez (Author)
I Blanco (Author)
C Lazaro (Author)
J Brunet (Author)
L Feliubadalo (Author)
C Cybulski (Author)
J Gronwald (Author)
K Durda (Author)
K Jaworska-Bieniek (Author)
G Sukiennicki (Author)
A Arason (Author)
J Chiquette (Author)
M R Teixeira (Author)
C Olswold (Author)
F J Couch (Author)
N M Lindor (Author)
X Wang (Author)
C I Szabo (Author)
K Offit (Author)
M Corines (Author)
L Jacobs (Author)
M E Robson (Author)
L Zhang (Author)
V Joseph (Author)
A Berger (Author)
C F Singer (Author)
C Rappaport (Author)
D G Kaulich (Author)
G Pfeiler (Author)
M K M Tea (Author)
C M Phelan (Author)
M H Greene (Author)
P L Mai (Author)
G Rennert (Author)
A M Mulligan (Author)
G Glendon (Author)
S Tchatchou (Author)
I L Andrulis (Author)
A E Toland (Author)
A Bojesen (Author)
I S Pedersen (Author)
M Thomassen (Author)
U B Jensen (Author)
Y Laitman (Author)
J Rantala (Author)
A Von Wachenfeldt (Author)
H Ehrencrona (Author)
M S Askmalm (Author)
A Borg (Author)
K B Kuchenbaecker (Author)
L McGuffog (Author)
D Barrowdale (Author)
S Healey (Author)
A Lee (Author)
P D P Pharoah (Author)
G Chenevix-Trench (Author)
A C Antoniou (Author)
E Friedman (Author)
Publication details: Cancer Epidemiology Biomarkers and Prevention, Vol.24(1), pp.308-316
Publisher: American Association for Cancer Research
Date published: 2015
DOI: 10.1158/1055-9965.EPI-14-0532
ISSN: 1055-9965; 1055-9965
Organisation Unit: Office of Research
Language: English
Record Identifier: 99451190102621
Output Type: Journal article

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