|
|
| PMID |
|
|
| TITLE |
|
| A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. |
|
| ABSTRACT |
|
|
|
| Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 × 10⁻⁹ to P(trend) = 3.9 × 10⁻⁷), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P(trend) = 1 × 10⁻⁷) to P(trend) = 8 × 10⁻⁵; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 × 10⁻⁷ |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2010/03/30 |
| accepted |
2010/08/26 |
| entrez |
2010/09/21 06:00 |
| pubmed |
2010/09/21 06:00 |
| medline |
2010/10/29 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Antoniou AC |
|
Antoniou |
Antonis C |
AC |
|
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. |
| Wang X |
|
Wang |
Xianshu |
X |
|
|
| Fredericksen ZS |
|
Fredericksen |
Zachary S |
ZS |
|
|
| McGuffog L |
|
McGuffog |
Lesley |
L |
|
|
| Tarrell R |
|
Tarrell |
Robert |
R |
|
|
| Sinilnikova OM |
|
Sinilnikova |
Olga M |
OM |
|
|
| Healey S |
|
Healey |
Sue |
S |
|
|
| Morrison J |
|
Morrison |
Jonathan |
J |
|
|
| Kartsonaki C |
|
Kartsonaki |
Christiana |
C |
|
|
| Lesnick T |
|
Lesnick |
Timothy |
T |
|
|
| Ghoussaini M |
|
Ghoussaini |
Maya |
M |
|
|
| Barrowdale D |
|
Barrowdale |
Daniel |
D |
|
|
|
EMBRACE |
|
|
|
|
|
| Peock S |
|
Peock |
Susan |
S |
|
|
| Cook M |
|
Cook |
Margaret |
M |
|
|
| Oliver C |
|
Oliver |
Clare |
C |
|
|
| Frost D |
|
Frost |
Debra |
D |
|
|
| Eccles D |
|
Eccles |
Diana |
D |
|
|
| Evans DG |
|
Evans |
D Gareth |
DG |
|
|
| Eeles R |
|
Eeles |
Ros |
R |
|
|
| Izatt L |
|
Izatt |
Louise |
L |
|
|
| Chu C |
|
Chu |
Carol |
C |
|
|
| Douglas F |
|
Douglas |
Fiona |
F |
|
|
| Paterson J |
|
Paterson |
Joan |
J |
|
|
| Stoppa-Lyonnet D |
|
Stoppa-Lyonnet |
Dominique |
D |
|
|
| Houdayer C |
|
Houdayer |
Claude |
C |
|
|
| Mazoyer S |
|
Mazoyer |
Sylvie |
S |
|
|
| Giraud S |
|
Giraud |
Sophie |
S |
|
|
| Lasset C |
|
Lasset |
Christine |
C |
|
|
| Remenieras A |
|
Remenieras |
Audrey |
A |
|
|
| Caron O |
|
Caron |
Olivier |
O |
|
|
| Hardouin A |
|
Hardouin |
Agnès |
A |
|
|
| Berthet P |
|
Berthet |
Pascaline |
P |
|
|
|
GEMO Study Collaborators |
|
|
|
|
|
| Hogervorst FB |
|
Hogervorst |
Frans B L |
FB |
|
|
| Rookus MA |
|
Rookus |
Matti A |
MA |
|
|
| Jager A |
|
Jager |
Agnes |
A |
|
|
| van den Ouweland A |
|
van den Ouweland |
Ans |
A |
|
|
| Hoogerbrugge N |
|
Hoogerbrugge |
Nicoline |
N |
|
|
| van der Luijt RB |
|
van der Luijt |
Rob B |
RB |
|
|
| Meijers-Heijboer H |
|
Meijers-Heijboer |
Hanne |
H |
|
|
| Gómez García EB |
|
Gómez García |
Encarna B |
EB |
|
|
|
HEBON |
|
|
|
|
|
| Devilee P |
|
Devilee |
Peter |
P |
|
|
| Vreeswijk MP |
|
Vreeswijk |
Maaike P G |
MP |
|
|
| Lubinski J |
|
Lubinski |
Jan |
J |
|
|
| Jakubowska A |
|
Jakubowska |
Anna |
A |
|
|
| Gronwald J |
|
Gronwald |
Jacek |
J |
|
|
| Huzarski T |
|
Huzarski |
Tomasz |
T |
|
|
| Byrski T |
|
Byrski |
Tomasz |
T |
|
|
| Górski B |
|
Górski |
Bohdan |
B |
|
|
| Cybulski C |
|
Cybulski |
Cezary |
C |
|
|
| Spurdle AB |
|
Spurdle |
Amanda B |
AB |
|
|
| Holland H |
|
Holland |
Helene |
H |
|
|
|
kConFab |
|
|
|
|
|
| Goldgar DE |
|
Goldgar |
David E |
DE |
|
|
| John EM |
|
John |
Esther M |
EM |
|
|
| Hopper JL |
|
Hopper |
John L |
JL |
|
|
| Southey M |
|
Southey |
Melissa |
M |
|
|
| Buys SS |
|
Buys |
Saundra S |
SS |
|
|
| Daly MB |
|
Daly |
Mary B |
MB |
|
|
| Terry MB |
|
Terry |
Mary-Beth |
MB |
|
|
| Schmutzler RK |
|
Schmutzler |
Rita K |
RK |
|
|
| Wappenschmidt B |
|
Wappenschmidt |
Barbara |
B |
|
|
| Engel C |
|
Engel |
Christoph |
C |
|
|
| Meindl A |
|
Meindl |
Alfons |
A |
|
|
| Preisler-Adams S |
|
Preisler-Adams |
Sabine |
S |
|
|
| Arnold N |
|
Arnold |
Norbert |
N |
|
|
| Niederacher D |
|
Niederacher |
Dieter |
D |
|
|
| Sutter C |
|
Sutter |
Christian |
C |
|
|
| Domchek SM |
|
Domchek |
Susan M |
SM |
|
|
| Nathanson KL |
|
Nathanson |
Katherine L |
KL |
|
|
| Rebbeck T |
|
Rebbeck |
Timothy |
T |
|
|
| Blum JL |
|
Blum |
Joanne L |
JL |
|
|
| Piedmonte M |
|
Piedmonte |
Marion |
M |
|
|
| Rodriguez GC |
|
Rodriguez |
Gustavo C |
GC |
|
|
| Wakeley K |
|
Wakeley |
Katie |
K |
|
|
| Boggess JF |
|
Boggess |
John F |
JF |
|
|
| Basil J |
|
Basil |
Jack |
J |
|
|
| Blank SV |
|
Blank |
Stephanie V |
SV |
|
|
| Friedman E |
|
Friedman |
Eitan |
E |
|
|
| Kaufman B |
|
Kaufman |
Bella |
B |
|
|
| Laitman Y |
|
Laitman |
Yael |
Y |
|
|
| Milgrom R |
|
Milgrom |
Roni |
R |
|
|
| Andrulis IL |
|
Andrulis |
Irene L |
IL |
|
|
| Glendon G |
|
Glendon |
Gord |
G |
|
|
| Ozcelik H |
|
Ozcelik |
Hilmi |
H |
|
|
| Kirchhoff T |
|
Kirchhoff |
Tomas |
T |
|
|
| Vijai J |
|
Vijai |
Joseph |
J |
|
|
| Gaudet MM |
|
Gaudet |
Mia M |
MM |
|
|
| Altshuler D |
|
Altshuler |
David |
D |
|
|
| Guiducci C |
|
Guiducci |
Candace |
C |
|
|
|
SWE-BRCA |
|
|
|
|
|
| Loman N |
|
Loman |
Niklas |
N |
|
|
| Harbst K |
|
Harbst |
Katja |
K |
|
|
| Rantala J |
|
Rantala |
Johanna |
J |
|
|
| Ehrencrona H |
|
Ehrencrona |
Hans |
H |
|
|
| Gerdes AM |
|
Gerdes |
Anne-Marie |
AM |
|
|
| Thomassen M |
|
Thomassen |
Mads |
M |
|
|
| Sunde L |
|
Sunde |
Lone |
L |
|
|
| Peterlongo P |
|
Peterlongo |
Paolo |
P |
|
|
| Manoukian S |
|
Manoukian |
Siranoush |
S |
|
|
| Bonanni B |
|
Bonanni |
Bernardo |
B |
|
|
| Viel A |
|
Viel |
Alessandra |
A |
|
|
| Radice P |
|
Radice |
Paolo |
P |
|
|
| Caldes T |
|
Caldes |
Trinidad |
T |
|
|
| de la Hoya M |
|
de la Hoya |
Miguel |
M |
|
|
| Singer CF |
|
Singer |
Christian F |
CF |
|
|
| Fink-Retter A |
|
Fink-Retter |
Anneliese |
A |
|
|
| Greene MH |
|
Greene |
Mark H |
MH |
|
|
| Mai PL |
|
Mai |
Phuong L |
PL |
|
|
| Loud JT |
|
Loud |
Jennifer T |
JT |
|
|
| Guidugli L |
|
Guidugli |
Lucia |
L |
|
|
| Lindor NM |
|
Lindor |
Noralane M |
NM |
|
|
| Hansen TV |
|
Hansen |
Thomas V O |
TV |
|
|
| Nielsen FC |
|
Nielsen |
Finn C |
FC |
|
|
| Blanco I |
|
Blanco |
Ignacio |
I |
|
|
| Lazaro C |
|
Lazaro |
Conxi |
C |
|
|
| Garber J |
|
Garber |
Judy |
J |
|
|
| Ramus SJ |
|
Ramus |
Susan J |
SJ |
|
|
| Gayther SA |
|
Gayther |
Simon A |
SA |
|
|
| Phelan C |
|
Phelan |
Catherine |
C |
|
|
| Narod S |
|
Narod |
Stephen |
S |
|
|
| Szabo CI |
|
Szabo |
Csilla I |
CI |
|
|
|
MOD SQUAD |
|
|
|
|
|
| Benitez J |
|
Benitez |
Javier |
J |
|
|
| Osorio A |
|
Osorio |
Ana |
A |
|
|
| Nevanlinna H |
|
Nevanlinna |
Heli |
H |
|
|
| Heikkinen T |
|
Heikkinen |
Tuomas |
T |
|
|
| Caligo MA |
|
Caligo |
Maria A |
MA |
|
|
| Beattie MS |
|
Beattie |
Mary S |
MS |
|
|
| Hamann U |
|
Hamann |
Ute |
U |
|
|
| Godwin AK |
|
Godwin |
Andrew K |
AK |
|
|
| Montagna M |
|
Montagna |
Marco |
M |
|
|
| Casella C |
|
Casella |
Cinzia |
C |
|
|
| Neuhausen SL |
|
Neuhausen |
Susan L |
SL |
|
|
| Karlan BY |
|
Karlan |
Beth Y |
BY |
|
|
| Tung N |
|
Tung |
Nadine |
N |
|
|
| Toland AE |
|
Toland |
Amanda E |
AE |
|
|
| Weitzel J |
|
Weitzel |
Jeffrey |
J |
|
|
| Olopade O |
|
Olopade |
Olofunmilayo |
O |
|
|
| Simard J |
|
Simard |
Jacques |
J |
|
|
| Soucy P |
|
Soucy |
Penny |
P |
|
|
| Rubinstein WS |
|
Rubinstein |
Wendy S |
WS |
|
|
| Arason A |
|
Arason |
Adalgeir |
A |
|
|
| Rennert G |
|
Rennert |
Gad |
G |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Chang-Claude J |
|
Chang-Claude |
Jenny |
J |
|
|
| Flesch-Janys D |
|
Flesch-Janys |
Dieter |
D |
|
|
| Brauch H |
|
Brauch |
Hiltrud |
H |
|
|
|
GENICA |
|
|
|
|
|
| Severi G |
|
Severi |
Gianluca |
G |
|
|
| Baglietto L |
|
Baglietto |
Laura |
L |
|
|
| Cox A |
|
Cox |
Angela |
A |
|
|
| Cross SS |
|
Cross |
Simon S |
SS |
|
|
| Miron P |
|
Miron |
Penelope |
P |
|
|
| Gerty SM |
|
Gerty |
Sue M |
SM |
|
|
| Tapper W |
|
Tapper |
William |
W |
|
|
| Yannoukakos D |
|
Yannoukakos |
Drakoulis |
D |
|
|
| Fountzilas G |
|
Fountzilas |
George |
G |
|
|
| Fasching PA |
|
Fasching |
Peter A |
PA |
|
|
| Beckmann MW |
|
Beckmann |
Matthias W |
MW |
|
|
| Dos Santos Silva I |
|
Dos Santos Silva |
Isabel |
I |
|
|
| Peto J |
|
Peto |
Julian |
J |
|
|
| Lambrechts D |
|
Lambrechts |
Diether |
D |
|
|
| Paridaens R |
|
Paridaens |
Robert |
R |
|
|
| Rüdiger T |
|
Rüdiger |
Thomas |
T |
|
|
| Försti A |
|
Försti |
Asta |
A |
|
|
| Winqvist R |
|
Winqvist |
Robert |
R |
|
|
| Pylkäs K |
|
Pylkäs |
Katri |
K |
|
|
| Diasio RB |
|
Diasio |
Robert B |
RB |
|
|
| Lee AM |
|
Lee |
Adam M |
AM |
|
|
| Eckel-Passow J |
|
Eckel-Passow |
Jeanette |
J |
|
|
| Vachon C |
|
Vachon |
Celine |
C |
|
|
| Blows F |
|
Blows |
Fiona |
F |
|
|
| Driver K |
|
Driver |
Kristy |
K |
|
|
| Dunning A |
|
Dunning |
Alison |
A |
|
|
| Pharoah PP |
|
Pharoah |
Paul P D |
PP |
|
|
| Offit K |
|
Offit |
Kenneth |
K |
|
|
| Pankratz VS |
|
Pankratz |
V Shane |
VS |
|
|
| Hakonarson H |
|
Hakonarson |
Hakon |
H |
|
|
| Chenevix-Trench G |
|
Chenevix-Trench |
Georgia |
G |
|
|
| Easton DF |
|
Easton |
Douglas F |
DF |
|
|
| Couch FJ |
|
Couch |
Fergus J |
FJ |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 42 |
| ISSUE: 10 |
| TITLE: Nature genetics |
| ISOABBREVIATION: Nat Genet |
| YEAR: 2010 |
| MONTH: Oct |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1546-1718 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Nat Genet |
| COUNTRY: United States |
| ISSNLINKING: 1061-4036 |
| NLMUNIQUEID: 9216904 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Comparative Study |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| CommentIn |
Nat Genet. 2010 Oct;42(10):819-20 |
20877320 |
|
| CommentIn |
Nat Rev Cancer. 2010 Nov;10(11):743 |
21080600 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| U01 CA069417 |
NCI NIH HHS |
United States |
| U01 CA069638 |
NCI NIH HHS |
United States |
| CA128978 |
NCI NIH HHS |
United States |
|
Wellcome Trust |
United Kingdom |
| RC4 CA153828 |
NCI NIH HHS |
United States |
| 11174 |
Cancer Research UK |
United Kingdom |
| U01 CA069398 |
NCI NIH HHS |
United States |
| A10119 |
Cancer Research UK |
United Kingdom |
| R01 CA128978 |
NCI NIH HHS |
United States |
| U01 CA069631 |
NCI NIH HHS |
United States |
| M01 RR000043 |
NCRR NIH HHS |
United States |
| A10124 |
Cancer Research UK |
United Kingdom |
| 10124 |
Cancer Research UK |
United Kingdom |
| 11022 |
Cancer Research UK |
United Kingdom |
| P50 CA089393 |
NCI NIH HHS |
United States |
| P50 CA116201 |
NCI NIH HHS |
United States |
| G0801875 |
Medical Research Council |
United Kingdom |
| U01 CA113916 |
NCI NIH HHS |
United States |
| P50 CA083638 |
NCI NIH HHS |
United States |
| R01 CA122340 |
NCI NIH HHS |
United States |
| R01 CA074415 |
NCI NIH HHS |
United States |
| 10118 |
Cancer Research UK |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| BRCA1 Protein |
genetics |
| Breast Neoplasms |
pathology |
| Case-Control Studies |
pathology |
| Chromosomes, Human, Pair 19 |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genotype |
genetics |
| Humans |
genetics |
| Mutation |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Receptor, ErbB-2 |
genetics |
| Receptors, Estrogen |
genetics |
| Receptors, Progesterone |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
BRCA1 Protein |
| 0 |
Receptors, Estrogen |
| 0 |
Receptors, Progesterone |
| EC 2.7.10.1 |
ERBB2 protein, human |
| EC 2.7.10.1 |
Receptor, ErbB-2 |
|
| OTHER ID's |
|
|
|
