Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24325915
TITLE
Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.
ABSTRACT
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.
DATE PUBLISHED
2014 May
HISTORY
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
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
INVESTIGATORS
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