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| PMID |
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| TITLE |
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| Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. |
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| ABSTRACT |
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| Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| aheadofprint |
2013/12/09 |
| aheadofprint |
2014/01/23 |
| entrez |
2013/12/12 06:00 |
| pubmed |
2013/12/12 06:00 |
| medline |
2014/06/25 06:00 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Purrington KS |
|
Purrington |
Kristen S |
KS |
|
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. |
| Slager S |
|
Slager |
Susan |
S |
|
|
| Eccles D |
|
Eccles |
Diana |
D |
|
|
| Yannoukakos D |
|
Yannoukakos |
Drakoulis |
D |
|
|
| Fasching PA |
|
Fasching |
Peter A |
PA |
|
|
| Miron P |
|
Miron |
Penelope |
P |
|
|
| Carpenter J |
|
Carpenter |
Jane |
J |
|
|
| Chang-Claude J |
|
Chang-Claude |
Jenny |
J |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Kristensen V |
|
Kristensen |
Vessela |
V |
|
|
| Anton-Culver H |
|
Anton-Culver |
Hoda |
H |
|
|
| Goodfellow P |
|
Goodfellow |
Paul |
P |
|
|
| Tapper WJ |
|
Tapper |
William J |
WJ |
|
|
| Rafiq S |
|
Rafiq |
Sajjad |
S |
|
|
| Gerty SM |
|
Gerty |
Susan M |
SM |
|
|
| Durcan L |
|
Durcan |
Lorraine |
L |
|
|
| Konstantopoulou I |
|
Konstantopoulou |
Irene |
I |
|
|
| Fostira F |
|
Fostira |
Florentia |
F |
|
|
| Vratimos A |
|
Vratimos |
Athanassios |
A |
|
|
| Apostolou P |
|
Apostolou |
Paraskevi |
P |
|
|
| Konstanta I |
|
Konstanta |
Irene |
I |
|
|
| Kotoula V |
|
Kotoula |
Vassiliki |
V |
|
|
| Lakis S |
|
Lakis |
Sotiris |
S |
|
|
| Dimopoulos MA |
|
Dimopoulos |
Meletios A |
MA |
|
|
| Skarlos D |
|
Skarlos |
Dimosthenis |
D |
|
|
| Pectasides D |
|
Pectasides |
Dimitrios |
D |
|
|
| Fountzilas G |
|
Fountzilas |
George |
G |
|
|
| Beckmann MW |
|
Beckmann |
Matthias W |
MW |
|
|
| Hein A |
|
Hein |
Alexander |
A |
|
|
| Ruebner M |
|
Ruebner |
Matthias |
M |
|
|
| Ekici AB |
|
Ekici |
Arif B |
AB |
|
|
| Hartmann A |
|
Hartmann |
Arndt |
A |
|
|
| Schulz-Wendtland R |
|
Schulz-Wendtland |
Ruediger |
R |
|
|
| Renner SP |
|
Renner |
Stefan P |
SP |
|
|
| Janni W |
|
Janni |
Wolfgang |
W |
|
|
| Rack B |
|
Rack |
Brigitte |
B |
|
|
| Scholz C |
|
Scholz |
Christoph |
C |
|
|
| Neugebauer J |
|
Neugebauer |
Julia |
J |
|
|
| Andergassen U |
|
Andergassen |
Ulrich |
U |
|
|
| Lux MP |
|
Lux |
Michael P |
MP |
|
|
| Haeberle L |
|
Haeberle |
Lothar |
L |
|
|
| Clarke C |
|
Clarke |
Christine |
C |
|
|
| Pathmanathan N |
|
Pathmanathan |
Nirmala |
N |
|
|
| Rudolph A |
|
Rudolph |
Anja |
A |
|
|
| Flesch-Janys D |
|
Flesch-Janys |
Dieter |
D |
|
|
| Nickels S |
|
Nickels |
Stefan |
S |
|
|
| Olson JE |
|
Olson |
Janet E |
JE |
|
|
| Ingle JN |
|
Ingle |
James N |
JN |
|
|
| Olswold C |
|
Olswold |
Curtis |
C |
|
|
| Slettedahl S |
|
Slettedahl |
Seth |
S |
|
|
| Eckel-Passow JE |
|
Eckel-Passow |
Jeanette E |
JE |
|
|
| Anderson SK |
|
Anderson |
S Keith |
SK |
|
|
| Visscher DW |
|
Visscher |
Daniel W |
DW |
|
|
| Cafourek VL |
|
Cafourek |
Victoria L |
VL |
|
|
| Sicotte H |
|
Sicotte |
Hugues |
H |
|
|
| Prodduturi N |
|
Prodduturi |
Naresh |
N |
|
|
| Weiderpass E |
|
Weiderpass |
Elisabete |
E |
|
|
| Bernstein L |
|
Bernstein |
Leslie |
L |
|
|
| Ziogas A |
|
Ziogas |
Argyrios |
A |
|
|
| Ivanovich J |
|
Ivanovich |
Jennifer |
J |
|
|
| Giles GG |
|
Giles |
Graham G |
GG |
|
|
| Baglietto L |
|
Baglietto |
Laura |
L |
|
|
| Southey M |
|
Southey |
Melissa |
M |
|
|
| Kosma VM |
|
Kosma |
Veli-Matti |
VM |
|
|
| Fischer HP |
|
Fischer |
Hans-Peter |
HP |
|
|
|
GENICA Network |
|
|
|
|
|
| Reed MW |
|
Reed |
Malcom W R |
MW |
|
|
| Cross SS |
|
Cross |
Simon S |
SS |
|
|
| Deming-Halverson S |
|
Deming-Halverson |
Sandra |
S |
|
|
| Shrubsole M |
|
Shrubsole |
Martha |
M |
|
|
| Cai Q |
|
Cai |
Qiuyin |
Q |
|
|
| Shu XO |
|
Shu |
Xiao-Ou |
XO |
|
|
| Daly M |
|
Daly |
Mary |
M |
|
|
| Weaver J |
|
Weaver |
Joellen |
J |
|
|
| Ross E |
|
Ross |
Eric |
E |
|
|
| Klemp J |
|
Klemp |
Jennifer |
J |
|
|
| Sharma P |
|
Sharma |
Priyanka |
P |
|
|
| Torres D |
|
Torres |
Diana |
D |
|
|
| Rüdiger T |
|
Rüdiger |
Thomas |
T |
|
|
| Wölfing H |
|
Wölfing |
Heidrun |
H |
|
|
| Ulmer HU |
|
Ulmer |
Hans-Ulrich |
HU |
|
|
| Försti A |
|
Försti |
Asta |
A |
|
|
| Khoury T |
|
Khoury |
Thaer |
T |
|
|
| Kumar S |
|
Kumar |
Shicha |
S |
|
|
| Pilarski R |
|
Pilarski |
Robert |
R |
|
|
| Shapiro CL |
|
Shapiro |
Charles L |
CL |
|
|
| Greco D |
|
Greco |
Dario |
D |
|
|
| Heikkilä P |
|
Heikkilä |
Päivi |
P |
|
|
| Aittomäki K |
|
Aittomäki |
Kristiina |
K |
|
|
| Blomqvist C |
|
Blomqvist |
Carl |
C |
|
|
| Irwanto A |
|
Irwanto |
Astrid |
A |
|
|
| Liu J |
|
Liu |
Jianjun |
J |
|
|
| Pankratz VS |
|
Pankratz |
Vernon Shane |
VS |
|
|
| Wang X |
|
Wang |
Xianshu |
X |
|
|
| Severi G |
|
Severi |
Gianluca |
G |
|
|
| Mannermaa A |
|
Mannermaa |
Arto |
A |
|
|
| Easton D |
|
Easton |
Douglas |
D |
|
|
| Hall P |
|
Hall |
Per |
P |
|
|
| Brauch H |
|
Brauch |
Hiltrud |
H |
|
|
| Cox A |
|
Cox |
Angela |
A |
|
|
| Zheng W |
|
Zheng |
Wei |
W |
|
|
| Godwin AK |
|
Godwin |
Andrew K |
AK |
|
|
| Hamann U |
|
Hamann |
Ute |
U |
|
|
| Ambrosone C |
|
Ambrosone |
Christine |
C |
|
|
| Toland AE |
|
Toland |
Amanda Ewart |
AE |
|
|
| Nevanlinna H |
|
Nevanlinna |
Heli |
H |
|
|
| Vachon CM |
|
Vachon |
Celine M |
CM |
|
|
| Couch FJ |
|
Couch |
Fergus J |
FJ |
|
|
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| INVESTIGATORS |
|
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| JOURNAL |
|
| VOLUME: 35 |
| ISSUE: 5 |
| TITLE: Carcinogenesis |
| ISOABBREVIATION: Carcinogenesis |
| YEAR: 2014 |
| MONTH: May |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2180 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Carcinogenesis |
| COUNTRY: England |
| ISSNLINKING: 0143-3334 |
| NLMUNIQUEID: 8008055 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| Cites |
Cancer Res. 1990 Dec 1;50(23):7710-6 |
2253214 |
|
| Cites |
PLoS One. 2013;8(5):e63925 |
23717510 |
|
| Cites |
J Clin Pathol. 2005 Apr;58(4):361-6 |
15790698 |
|
| Cites |
Cancer. 2007 May 1;109(9):1721-8 |
17387718 |
|
| Cites |
J Natl Cancer Inst. 2007 Nov 21;99(22):1695-705 |
18000216 |
|
| Cites |
Cancer Res. 2008 Feb 1;68(3):693-9 |
18245468 |
|
| Cites |
Breast Cancer Res Treat. 2008 May;109(1):123-39 |
17578664 |
|
| Cites |
Bioinformatics. 2008 Dec 15;24(24):2938-9 |
18974171 |
|
| Cites |
Cancer Res. 2009 Sep 15;69(18):7473-9 |
19723659 |
|
| Cites |
Breast Cancer Res Treat. 2009 Nov;118(1):131-7 |
19189211 |
|
| Cites |
N Engl J Med. 2010 Nov 11;363(20):1938-48 |
21067385 |
|
| Cites |
Hum Mol Genet. 2011 Aug 15;20(16):3289-303 |
21596841 |
|
| Cites |
Cancer Res. 2011 Oct 1;71(19):6240-9 |
21844186 |
|
| Cites |
Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2222-31 |
21795498 |
|
| Cites |
Hum Mol Genet. 2011 Dec 1;20(23):4693-706 |
21852249 |
|
| Cites |
BMC Dev Biol. 2011;11:65 |
22039763 |
|
| Cites |
Nat Genet. 2011 Dec;43(12):1210-4 |
22037553 |
|
| Cites |
Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 |
22064851 |
|
| Cites |
Cancer Res. 2012 Apr 1;72(7):1795-803 |
22331459 |
|
| Cites |
Nature. 2012 Sep 6;489(7414):57-74 |
22955616 |
|
| Cites |
Hum Mol Genet. 2012 Dec 15;21(24):5373-84 |
22976474 |
|
| Cites |
Nat Genet. 2013 Apr;45(4):353-61, 361e1-2 |
23535729 |
|
| Cites |
Nat Genet. 2013 Apr;45(4):371-84, 384e1-2 |
23535731 |
|
| Cites |
Nat Genet. 2013 Apr;45(4):392-8, 398e1-2 |
23535733 |
|
| Cites |
Cancer Res. 2013 Apr 1;73(7):2025-30 |
23536562 |
|
| Cites |
Am J Hum Genet. 2013 Apr 4;92(4):489-503 |
23540573 |
|
| Cites |
BMC Res Notes. 2013;6:33 |
23360712 |
|
| Cites |
Endocrinology. 2013 May;154(5):1780-93 |
23515291 |
|
| Cites |
JAMA. 1996 Aug 21;276(7):549-54 |
8709404 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 5U01CA113916 |
NCI NIH HHS |
United States |
| P30 CA015083 |
NCI NIH HHS |
United States |
| P30 CA168524 |
NCI NIH HHS |
United States |
| P30 CA168524 |
NCI NIH HHS |
United States |
| P50 CA116201 |
NCI NIH HHS |
United States |
| P50 CA116201 |
NCI NIH HHS |
United States |
| R01 CA077398 |
NCI NIH HHS |
United States |
| R01 CA128978 |
NCI NIH HHS |
United States |
| R01 CA128978 |
NCI NIH HHS |
United States |
| R01 CA140323 |
NCI NIH HHS |
United States |
| R01CA14032 |
NCI NIH HHS |
United States |
| R25 CA092049 |
NCI NIH HHS |
United States |
| R25 CA092049 |
NCI NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Case-Control Studies |
|
| Chromosomes, Human, Pair 19 |
|
| Estrogen Receptor alpha |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genome-Wide Association Study |
genetics |
| Humans |
genetics |
| Middle Aged |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Quantitative Trait Loci |
genetics |
| Triple Negative Breast Neoplasms |
genetics |
| Young Adult |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Estrogen Receptor alpha |
| 0 |
estrogen receptor alpha, human |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC4004200 |
NLM |
|
|
