These elevated HRs were similar to the corresponding ORs for association between the PRS and ER-negative (OR = 1.47) and ER-positive (OR = 1.74) breast cancer reported in the general population.12 The vast majority of individuals in the general population would be expected to be noncarriers with intact BRCA1/2 protein expression in at-risk tissues, so this observation suggests that some SNPs in the PRS may exert their effect on proteins that interact with stable wildtype or mutant BRCA1 or BRCA2 protein. This evidence concerns the gene BRCA2 and breast cancer.