Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

被引：401

作者：

Mavaddat, Nasim

Pharoah, Paul D. P. ^{[1
,2
]}

Michailidou, Kyriaki ^{[1
]}

Tyrer, Jonathan ^{[2
]}

Brook, Mark N. ^{[3
]}

Bolla, Manjeet K. ^{[1
]}

Wang, Qin ^{[1
]}

Dennis, Joe ^{[1
]}

Dunning, Alison M. ^{[2
]}

Shah, Mitul

Luben, Robert ^{[1
]}

Brown, Judith ^{[1
]}

Bojesen, Stig E. ^{[4
,5
,6
]}

Nordestgaard, Borge G. ^{[4
,5
,6
]}

Nielsen, Sune F. ^{[4
,5
]}

Flyger, Henrik ^{[7
]}

Czene, Kamila ^{[8
]}

Darabi, Hatef ^{[8
]}

Eriksson, Mikael ^{[8
]}

Peto, Julian ^{[9
]}

dos-Santos-Silva, Isabel ^{[9
]}

Dudbridge, Frank ^{[9
]}

Johnson, Nichola ^{[10
]}

Schmidt, Marjanka K. ^{[11
]}

Broeks, Annegien ^{[11
]}

Verhoef, Senno ^{[11
]}

Rutgers, Emiel J. ^{[11
]}

Swerdlow, Anthony ^{[3
,12
]}

Ashworth, Alan ^{[10
]}

Orr, Nick ^{[10
]}

Schoemaker, Minouk J. ^{[3
]}

Figueroa, Jonine ^{[13
]}

Chanock, Stephen J. ^{[13
]}

Brinton, Louise

Lissowska, Jolanta ^{[14
,15
]}

Couch, Fergus J. ^{[16
]}

Olson, Janet E. ^{[17
]}

Vachon, Celine ^{[17
]}

Pankratz, Vernon S. ^{[17
]}

Lambrechts, Diether ^{[18
,19
]}

Wildiers, Hans ^{[20
,21
]}

Van Ongeval, Chantal ^{[23
]}

Van Limbergen, Erik ^{[22
]}

Kristensen, Vessela

Alnaes, Grethe Grenaker ^{[24
]}

Nord, Silje ^{[24
]}

Borresen-Dale, Anne-Lise ^{[24
,25
]}

Nevanlinna, Heli ^{[27
,28
]}

Muranen, Taru A. ^{[27
,28
]}

Aittomaeki, Kristiina ^{[29
]}

机构：

[1] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[2] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England

[3] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England

[4] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark

[5] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark

[6] Copenhagen Univ Hosp, Fac Hlth & Med Sci, Herlev, Denmark

[7] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark

[8] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[9] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England

[10] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[11] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands

[12] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England

[13] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[14] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[15] Inst Oncol, Warsaw, Poland

[16] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[17] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[18] VIB, Vesalius Res Ctr, Leuven, Belgium

[19] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium

[20] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium

[21] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium

[22] Univ Hosp Gasthuisberg, Dept Radiat Oncol, Leuven, Belgium

[23] Univ Hosp Gasthuisberg, Dept Radiol, Leuven, Belgium

[24] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway

[25] Univ Oslo, Inst Clin Med, Oslo, Norway

[26] Univ Oslo, Dept Clin Mol Biol, Oslo, Norway

[27] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Hus, Finland

[28] Univ Helsinki, Cent Hosp, Helsinki, Hus, Finland

[29] Univ Helsinki, Dept Clin Genet, Helsinki, Hus, Finland

[30] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[31] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany

[32] Univ Erlangen Nurnberg, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Univ Hosp Erlangen,Comprehens Canc Ctr Erlangen E, D-91054 Erlangen, Germany

[33] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[34] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Erlangen, Germany

[35] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[36] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany

[37] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany

[38] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA

[39] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA

[40] Geisel Sch Med Dartmouth, Hanover, NH USA

[41] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL 33612 USA

[42] Harvard Univ, TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA

[43] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[44] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

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

[46] Inst Canc Res, Sect Canc Genet, London SW3 6JB, England

[47] Genome Inst Singapore, Div Human Genet, Singapore, Singapore

[48] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genotyping CEGEN Unit, Madrid, Spain

[49] Ctr Invest Red Enfermedades Raras, Valencia, Spain

[50] Hosp Univ La Paz, Serv Oncol Med, Madrid, Spain

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2015年 / 107卷 / 05期

基金：

加拿大健康研究院; 美国国家卫生研究院; 英国医学研究理事会; 瑞典研究理事会; 芬兰科学院; 俄罗斯基础研究基金会;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; FAMILY-HISTORY; PREVENTION; PROSTATE; SUBTYPES;

D O I：

10.1093/jnci/djv036

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

引用

页数：15

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