Validation of the BOADICEA model and a 313-variant polygenic risk score for breast cancer risk prediction in a Dutch prospective cohort.

Abstract

METHODS

Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS₃₁₃ was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS₃₁₃ and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS₃₁₃). C-statistics were used to evaluate discriminative ability.

CONCLUSIONS

The effect size of the PRS₃₁₃ is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population.

PURPOSE

We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)-associated variants (PRS₃₁₃) and other, nongenetic risk factors.

RESULTS

In total, 320 women developed BC. The PRS₃₁₃ was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40-1.73]). Using 10-year risk estimates including age and the PRS₃₁₃, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653.