Percent mammographic density (PMD) adjusted for age and BMI is one of the strongest risk factors for breast cancer and is known to be approximately 60 percent heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD.

We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age- and body mass index-adjusted PMD. Our final data set included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1M platform. Principal component analysis (PCA) and identity-by-descent (IBD) analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD.

Women of Ashkenazi Jewish ancestry, as defined by the first principal component (PC1) of PCA and identity-by-descent analyses, represented approximately 15 percent of the sample. Ashkenazi Jewish ancestry, defined by PC1, was associated with higher adjusted PMD (p = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association.

Women of Ashkenazi Jewish ancestry based on genetic analysis are more likely to have high age- and BMI-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density.