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MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in six miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women's Circle of Health Study. Allele frequencies of most SNPs (87 %) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51 % increased risk in AAs (OR = 1.51, 95 % CI = 1.30-1.74, p = 3.3 × 10(-8)) and a 73 % increased risk in EAs (OR = 1.73, 95 % CI = 1.45-2.06, p = 1.4 × 10(-9)). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.

Genetic variants in microRNAs and breast cancer risk in African American and European American women