Prospective evaluation of a breast-cancer risk model integrating classical risk factors and polygenic risk in 15 cohorts from six countries
Prospective evaluation of a breast-cancer risk model integrating classical risk factors and polygenic risk in 15 cohorts from six countries
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DOI：
10.1093/ije/dyab036
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发表时间：
2021-03-23
影响因子：
7.7
通讯作者：
Chatterjee, Nilanjan
中科院分区：
文献类型：
--
作者：
Hurson, Amber N.;Choudhury, Parichoy Pal;Chatterjee, Nilanjan
Background: Rigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk.Methods: Fifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19-75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50-70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds.Results: Among women = 50 years old, these were 1.0 (0.7-1.3) and 1.2 (0.7-1.6), respectively. The proportion of women identified above a 3% 5-year risk threshold (used for recommending risk-reducing medications in the USA) ranged from 7.0% in Germany (similar to 841 000 of 12 million) to 17.7% in the USA (similar to 5.3 of 30 million). At this threshold, 14.7% of US women were reclassified by adding the PRS to classical risk factors, with identification of 12.2% of additional future cases.Conclusion: Integrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines.
