SNPs and breast cancer risk prediction for African American and Hispanic women

Richard Allman, Gillian S. Dite, John L. Hopper, Ora Gordon, Athena Starlard-Davenport, Rowan Chlebowski, Charles Kooperberg

For African American or Hispanic women, the extent to which clinical breast cancer risk prediction models are improved by including information on susceptibility single nucleotide polymorphisms (SNPs) is unknown, even though these women comprise increasing proportions of the US population and represent a large proportion of the world's population. We studied 7539 African American and 3363 Hispanic women from the Women's Health Initiative. The age-adjusted 5-year risks from the BCRAT and IBIS risk prediction models were measured and combined with a risk score based on >70 independent susceptibility SNPs. Logistic regression, adjusting for age group, was used to estimate risk associations with log-transformed age-adjusted 5-year risks. Discrimination was measured by the odds ratio (OR) per standard deviation (SD) and the area under the receiver operator curve (AUC). When considered alone, the ORs for African American women were 1.28 for BCRAT, and 1.04 for IBIS. When combined with the SNP risk score (OR 1.23), the corresponding ORs were 1.39 and 1.22. For Hispanic women the corresponding ORs were 1.25 for BCRAT, and 1.15 for IBIS. When combined with the SNP risk score (OR 1.39), the corresponding ORs were 1.48 and 1.42. There was no evidence that any of the combined models were not well calibrated. Including information on known breast cancer susceptibility loci provides approximately 10 and 19 % improvement in risk prediction using BCRAT for African Americans and Hispanics, respectively. The corresponding figures for IBIS are approximately 18 and 26 %, respectively.