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

Wanqing Wen,Jirong Long,Manjeet K Bolla,Jacques Simard,Keitaro Matsuo,Joe Dennis,Daehee Kang,Ying Zheng,Suleeporn Sangrajrang,Paul Brennan,Anna H Wu,Alison M Dunning,Douglas F Easton,Xingyi Guo,Qiuyin Cai,Hui Miao,Kyriaki Michailidou,Hidemi Ito,Ji-Yeob Choi,Per Hall,Qin Wang,Artitaya Lophatananon,Mikael Hartman,Chiu-Chen Tseng,Kenneth Muir,Cheng Har Yip,Chen‐Yang Shen ,Montserrat García‐Closas ,Paul D.p Pharoah ,Yong‐Bing Xiang ,Xiao‐Ou Shu ,Yu‐Tang Gao ,Soo‐Hwang Teo ,Shou‐Tung Chen ,Zheng Wang

doi:10.1186/s13058-016-0786-1

Abstract

BackgroundApproximately 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.MethodsWe 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.ResultsWe 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.ConclusionApproximately 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0786-1) contains supplementary material, which is available to authorized users.

Highlights

100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS)
The polygenic risk score (PRS) was derived based on the effect (β) and the number of risk alleles of a Single nucleotide polymorphism (SNP) carried by a woman
We have shown that known common genetic variants are important predictors for breast cancer risk, and using a 44-SNP PRS could help discriminate breast cancer risk in women of East Asian ancestry, the discriminatory ability is not sufficient for clinical application

Summary

Introduction

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. We confirmed a significant association in East Asian women for 31 of the 67 independent breast cancer susceptibility loci reported from previous GWAS conducted mostly in European descendants [13]. A relatively small study with 411 breast cancer cases and 1212 controls conducted in Singapore Chinese participants reported that a PRS constructed from 51 SNPs improved the classification of 6.2% of the women for their absolute risk of breast cancer in the 5 years [14]

Methods

Results

Discussion

Conclusion