Abstract
IntroductionGenetic variants for breast cancer risk identified in genome-wide association studies (GWAS) in Western populations require further testing in Asian populations. A risk assessment model incorporating both validated genetic variants and established risk factors may improve its performance in risk prediction of Asian women.MethodsA nested case-control study of female breast cancer (411 cases and 1,212 controls) within the Singapore Chinese Health Study was conducted to investigate the effects of 51 genetic variants identified in previous GWAS on breast cancer risk. The independent effect of these genetic variants was assessed by creating a summed genetic risk score (GRS) after adjustment for body mass index and the Gail model risk factors for breast cancer.ResultsThe GRS was an independent predictor of breast cancer risk in Chinese women. The multivariate-adjusted odds ratios (95% confidence intervals) of breast cancer for the second, third, and fourth quartiles of the GRS were 1.26 (0.90 to 1.76), 1.47 (1.06 to 2.04) and 1.75 (1.27 to 2.41) respectively (P for trend <0.001). In addition to established risk factors, the GRS improved the classification of 6.2% of women for their absolute risk of breast cancer in the next five years.ConclusionsGenetic variants on top of conventional risk factors can improve the risk prediction of breast cancer in Chinese women.
Highlights
Genetic variants for breast cancer risk identified in genome-wide association studies (GWAS) in Western populations require further testing in Asian populations
Study subjects The subjects included in this study are women enrolled in the Singapore Chinese Health Study (SCHS), a populationbased cohort study which has been described in detail previously [40]
We have evaluated a total of 51 single nucleotide polymorphism (SNP) and constructed a genetic risk score (GRS) to reflect their cumulative effect on breast cancer risk
Summary
Genetic variants for breast cancer risk identified in genome-wide association studies (GWAS) in Western populations require further testing in Asian populations. A risk assessment model incorporating both validated genetic variants and established risk factors may improve its performance in risk prediction of Asian women. Breast cancer is a heterogeneous disease that is associated with genetic and environmental factors. Investigations have mainly revolved around the presence of a family history, hormonal and reproductiverelated risk factors [1,2,3] with the effects of other lifestyle factors being queried recently. The risk of disease has been shown to increase with a woman’s age, age at menopause, age at first live birth, previous occurrence of atypical hyperplasia and family history [4]. The Gail model is the most widely used for breast cancer risk prediction. Most of the models are still lacking in their predictive ability [24,25,26,27] and may be inapplicable to Chinese populations
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