Hormone-dependent cancers (HDCs) share several risk factors, suggesting a common aetiology. Using data from genome-wide association studies, we showed spatial clustering of risk variants across four HDCs (breast, endometrial, ovarian and prostate cancers), contrasting with genetically uncorrelated traits. We identified 44 multi-HDC risk regions across the genome, defined as overlapping risk regions for at least two HDCs: two regions contained risk variants for all four HDCs, 13 for three HDCs and 28 for two HDCs. Integrating GWAS data, epigenomic profiling and promoter capture HiC maps from diverse cell line models, we annotated 53 candidate risk genes at 22 multi-HDC risk regions. These targets were enriched for established genes from the COSMIC Cancer Gene Census, but many had no previously reported pleiotropic roles. Additionally, we pinpointed lncRNAs as potential HDC targets and identified risk alleles in several regions that altered transcription factors motifs, suggesting regula...
| Authors | Rivera, IS; French, JD; Bitar, M; Sivakumaran, H; Nair, S; Kaufmann, S; Hillman, KM; Moradi Marjaneh, M; Beesley, J; Edwards, SL |
|---|---|
| Journal | PLOS GENETICS |
| Pages | e1011490 |
| Volume | 20 |
| Date | 25/12/2024 |
| Grant ID | |
| Funding Body | |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1371/journal.pgen.1011490 |