Genome wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with the risk of breast, ovarian, endometrial and prostate cancer. These genetic variants are typically dispersed across the human genome. However, we have identified 51 genomic regions that harbour risk SNPs for two or more of these cancer types, suggesting a common mechanism underlying their susceptibility. In this proposal, we will use Capture Hi-C technology to comprehensively identify the target genes at all 51 multi-cancer risk regions. We will then determine the mechanisms by which causal SNPs influence gene expression and prioritise key targets for future drug repositioning or drug development.
SNPs in multi-cancer risk regions modulate tissue-specific enhancers resulting in changes in expression of common target genes.
- To identify the target genes at multi-cancer risk regions using Capture Hi-C.
- To determine how the risk SNPs affects the expression of the target genes.
Outcomes and Significance
Hormone-related cancers represent a major health and economic burden. Collectively, breast, ovarian, endometrial and prostate cancers accounted for more than 28% of all cancers diagnosed in Australia last year. This project will identify the key genes responsible for risk of multiple cancers. Identifying the mechanism driving these multi-cancer risk regions will shed new light on the shared biology underlying hormone-related cancers and are likely to represent promising targets for the implicated cancers, or provide drug repositioning opportunities in cases where a drug is already available.