We previously reported a +ACA polymorphism in the minimal BRCA1 promoter region located -600bp from the exon 1a start site (ACATAACAC to ACATAA̱C1A̱ACAC). To determine the frequency of the +ACA in the general population, we genotyped 350 randomly selected women of child-bearing age with no history of breast cancer. Among this cohort, 191/350 (55%) individuals carried at least one polymorphic allele, the allelic frequency was determined to be 32% (226/700), and BRCA1 promoter genotypes (159/350, 45% wt/wt; 156/350, 45% wt/+ACA; and 35/350, 10% +ACA/+ACA) conformed to the Hardy-Weinberg equlibrium. Among breast cancer patients, 33/62 (53%) carried at least one polymorphic allele, and the allelic frequency was determined to be 45/124 (36%), similar to the frequency observed in the general population. However, the genotype distribution (29/62, 47% wt/wt; 21/62, 34% wt/+ACA; and 12/62, 19% +ACA/+ACA) did not conform to the Hardy-Weinberg equilibrium and was significantly different from that of the general population (P = 0.0043). These results suggest that the +ACA BRCA1 promoter polymorphism occurs frequently in the general population and may confer increased susceptibility to breast carcinogenesis. [ABSTRACT FROM AUTHOR]