Application values of genome-wide association studies in screening for breast cancer / 中华流行病学杂志

ABSTRACT

Objective@#To investigate the potential application values of screening on breast cancer, using the single-nucleotide polymorphisms (SNPs) that were identified from the genome- wide association studies (GWASs).@*Methods@#Two million Chinese women aged 35-69 years were simulated, based on both age distributions, age-specific incidence rates of breast cancer and the distribution of known risk factors, in 2013. Twenty-three SNPs identified from GWAS were further simulated. Both genetic-related risks explained by each SNPs and the improvement on the risks under reclassification, were used to select SNPs for the prediction on breast cancer among the targeted high-risk population. Further analyses were conducted to investigate the following items as improvements on detection rates of breast cancer among the high-risk populations, areas under the curve (AUC) and the odds ratio (OR) among women at high risk.@*Results@#A total of 12 SNPs were eligible for targeting the high-risk population of breast cancer. When high-risk populations were defined as women whose predicted risks were higher than the 95th predicted risk of the whole population, the detection rate (146.99/100 000) among high-risked women predicted by 12 SNPs would be significantly lower than 177.46/100 000, which was predicted by the known risk factors (P<0.001), among the high-risked women. Among those women at high risk, the detection rate (229.00/100 000) predicted by integrating known risk factors and 12 SNPs was significantly higher than that predicted by known risk factors (P<0.001). Also, the AUC increased from 64.4% to 67.8% (P<0.001), and the OR of increased from 3.32 to 4.33, predicted by integrating known risk factors and 12 SNPs, for women at high risk on breast cancer.@*Conclusion@#Targeted SNPs that were identified from genome- wide association studies could be used to improve the detection rates as well as the overall accuracy of risk prediction so as to identify the potential high-risk women on breast cancer before carrying on the screening program.