Performance of Common Genetic Variants in Breast-Cancer Risk Models.

被引：323

作者：

Wacholder, Sholom ^{[1
]}

Hartge, Patricia ^{[1
]}

Prentice, Ross ^{[3
]}

Garcia-Closas, Montserrat ^{[1
]}

Feigelson, Heather Spencer ^{[4
,5
]}

Diver, W. Ryan ^{[4
]}

Thun, Michael J. ^{[4
]}

Cox, David G. ^{[6
,7
]}

Hankinson, Susan E. ^{[7
,9
,10
]}

Kraft, Peter ^{[7
]}

Rosner, Bernard ^{[8
,9
,10
]}

Berg, Christine D. ^{[2
]}

Brinton, Louise A. ^{[1
]}

Lissowska, Jolanta ^{[11
,12
]}

Sherman, Mark E. ^{[1
]}

Chlebowski, Rowan ^{[13
]}

Kooperberg, Charles ^{[3
]}

Jackson, Rebecca D. ^{[14
]}

Buckman, Dennis W. ^{[15
]}

Hui, Peter ^{[15
]}

Pfeiffer, Ruth ^{[1
]}

Jacobs, Kevin B. ^{[1
]}

Thomas, Gilles D. ^{[1
]}

Hoover, Robert N. ^{[1
]}

Gail, Mitchell H. ^{[1
]}

Chanock, Stephen J. ^{[1
]}

Hunter, David J. ^{[7
,9
,10
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[2] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA

[3] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[4] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA

[5] Kaiser Permanente, Inst Hlth Res, Denver, CO USA

[6] INSERM, F-69008 Lyon, France

[7] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[12] Inst Oncol, Warsaw, Poland

[13] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Hematol & Med Oncol, Torrance, CA 90509 USA

[14] Ohio State Univ, Columbus, OH 43210 USA

[15] Informat Management Serv Inc, Silver Spring, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 362卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; POLYMORPHISMS; PREVENTION; ALLELES; MARKER;

D O I：

10.1056/NEJMoa0907727

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Genomewide association studies have identified multiple genetic variants associated with breast cancer. The extent to which these variants add to existing risk-assessment models is unknown. Methods: We used information on traditional risk factors and 10 common genetic variants associated with breast cancer in 5590 case subjects and 5998 control subjects, 50 to 79 years of age, from four U.S. cohort studies and one case-control study from Poland to fit models of the absolute risk of breast cancer. With the use of receiver-operating-characteristic curve analysis, we calculated the area under the curve (AUC) as a measure of discrimination. By definition, random classification of case and control subjects provides an AUC of 50%; perfect classification provides an AUC of 100%. We calculated the fraction of case subjects in quintiles of estimated absolute risk after the addition of genetic variants to the traditional risk model. Results: The AUC for a risk model with age, study and entry year, and four traditional risk factors was 58.0%; with the addition of 10 genetic variants, the AUC was 61.8%. About half the case subjects (47.2%) were in the same quintile of risk as in a model without genetic variants; 32.5% were in a higher quintile, and 20.4% were in a lower quintile. Conclusions: The inclusion of newly discovered genetic factors modestly improved the performance of risk models for breast cancer. The level of predicted breast-cancer risk among most women changed little after the addition of currently available genetic information. N Engl J Med 2010;362:986-93.

引用

页码：986 / 993

页数：8

共 31 条

[31] MODERATE ALCOHOL-CONSUMPTION AND THE RISK OF BREAST-CANCER [J].

WILLETT, WC ;

STAMPFER, MJ ;

COLDITZ, GA ;

ROSNER, BA ;

HENNEKENS, CH ;

SPEIZER, FE .

NEW ENGLAND JOURNAL OF MEDICINE, 1987, 316 (19) :1174-1180

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