Certain genetic variants are associated with risks of multiple
cancers. We investigated
breast cancer risk with overall
genetic susceptibility to each of 16 other
cancers. We constructed
polygenic risk scores (PRS) for 16
cancers using risk variants identified by genome-wide association studies. We evaluated the associations of these PRSs with
breast cancer risk (overall and by subtypes) using
Breast Cancer Association Consortium data, including 106,278 cases and 91,477 controls of European ancestry. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated to measure the association of each PRS with
breast cancer risk. Data from the UK Biobank, including 4,337 cases and 209,983 non-cases, were used to replicate the findings. A 5%-8% significantly elevated risk of overall
breast cancer was associated with per unit increase of the PRS for
glioma and
cancers of the corpus uteri, stomach, or colorectum. Analyses by subtype revealed that the PRS for corpus uteri
cancer (OR = 1.09; 95% CI, 1.03-1.15) and
stomach cancer (OR = 1.07; 95% CI, 1.03-1.12) were associated with
estrogen receptor-positive
breast cancer, while
ovarian cancer PRS was associated with
triple-negative breast cancer (OR = 1.25; 95% CI, 1.01-1.55). UK Biobank data supported the positive associations of overall
breast cancer risk with PRS for
melanoma and
cancers of the stomach, colorectum, and ovary. Our study provides strong evidence for shared
genetic susceptibility of
breast cancer with several other
cancers. Results from our study help uncover the genetic basis for breast and other
cancers and identify individuals at high risk for multiple
cancers.