BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors

被引：454

作者：

Lee, Andrew ^{[1
]}

Mavaddat, Nasim ^{[1
]}

Wilcox, Amber N. ^{[2
]}

Cunningham, Alex P. ^{[1
]}

Carver, Tim ^{[1
]}

Hartley, Simon ^{[1
]}

de Villiers, Chantal Babb ^{[3
]}

Izquierdo, Angel ^{[4
,5
]}

Simard, Jacques ^{[6
]}

Schmidt, Marjanka K. ^{[7
]}

Walter, Fiona M. ^{[3
]}

Chatterjee, Nilanjan ^{[8
,9
]}

Garcia-Closas, Montserrat ^{[2
]}

Tischkowitz, Marc ^{[10
,11
]}

Pharoah, Paul ^{[1
,12
]}

Easton, Douglas F. ^{[1
,12
]}

Antoniou, Antonis C. ^{[1
]}

机构：

[1] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England

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

[3] Univ Cambridge, Dept Publ Hlth & Primary Care, Primary Care Unit, Cambridge, England

[4] Girona Biomed Res Inst IdiBGi, Catalan Inst Oncol, Epidemiol Unit, Hereditary Canc Program, Girona, Spain

[5] Girona Biomed Res Inst IdiBGi, Catalan Inst Oncol, Girona Canc Registry, Girona, Spain

[6] Univ Laval, Res Ctr, Ctr Hosp Univ Quebec, Quebec City, PQ, Canada

[7] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands

[8] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[9] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[10] Univ Cambridge, Dept Med Genet, Cambridge, England

[11] Univ Cambridge, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England

[12] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

来源：

GENETICS IN MEDICINE | 2019年 / 21卷 / 08期

基金：

英国惠康基金; 欧洲研究理事会; 加拿大健康研究院;

关键词：

breast cancer; risk prediction; BOADICEA; rare variants; PRS; TRUNCATING VARIANTS; WOMEN; SUSCEPTIBILITY; OVARIAN; MUTATION; BRCA2; PALB2; MODIFIERS; MENOPAUSE; CHEK2;

D O I：

10.1038/s41436-018-0406-9

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs). Methods: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information. Results: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of >= 17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of >= 30% (high risk). Conclusion: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

引用

页码：1708 / 1718

页数：11

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