Validation of a genetic risk score for Arkansas women of color.

Abstract

African American women in the state of Arkansas have high breast cancer mortality rates. Breast cancer risk assessment tools developed for African American underestimate breast cancer risk. Combining African American breast cancer associated single-nucleotide polymorphisms (SNPs) into breast cancer risk algorithms may improve individualized estimates of a woman's risk of developing breast cancer and enable improved recommendation of screening and chemoprevention for women at high risk. The goal of this study was to confirm with an independent dataset consisting of Arkansas women of color, whether a genetic risk score derived from common breast cancer susceptibility SNPs can be combined with a clinical risk estimate provided by the Breast Cancer Risk Assessment Tool (BCRAT) to produce a more accurate individualized breast cancer risk estimate. A population-based cohort of African American women representative of Arkansas consisted of 319 cases and 559 controls for this study. Five-year and lifetime risks from the BCRAT were measured and combined with a risk score based on 75 independent susceptibility SNPs in African American women. We used the odds ratio (OR) per adjusted standard deviation to evaluate the improvement in risk estimates produced by combining the polygenic risk score (PRS) with 5-year and lifetime risk scores estimated using BCRAT. For 5-year risk OR per standard deviation increased from 1.84 to 2.08 with the addition of the polygenic risk score and from 1.79 to 2.07 for the lifetime risk score. Reclassification analysis indicated that 13% of cases had their 5-year risk increased above the 1.66% guideline threshold (NRI = 0.020 (95% CI -0.040, 0.080)) and 6.3% of cases had their lifetime risk increased above the 20% guideline threshold by the addition of the polygenic risk score (NRI = 0.034 (95% CI 0.000, 0.070)). Our data confirmed that discriminatory accuracy of BCRAT is improved for African American women in Arkansas with the inclusion of specific SNP breast cancer risk alleles.