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Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

Abstract：

BACKGROUND:Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. METHODS:We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. RESULTS:We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. CONCLUSION:Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Wen W,Shu XO,Guo X,Cai Q,Long J,Bolla MK,Michailidou K,Dennis J,Wang Q,Gao YT,Zheng Y,Dunning AM,García-Closas M,Brennan P,Chen ST,Choi JY,Hartman M,Ito H,Lophatananon A,Matsuo K,Miao H,Muir K,Sangrajrang S,

doi

10.1186/s13058-016-0786-1

subject

Has Abstract

pub_date

2016-12-08 00:00:00

pages

124

issue

1

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-016-0786-1

journal_volume

18

pub_type

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