More than 20,000 men are diagnosed annually with prostate cancer in Australia, yet prognosis and treatment lack sensitivity and specificity, creating challenges involving early detection and determining likelihood of metastasis. A family history of prostate cancer has consistently been identified as a major risk factor and genome wide association studies have identified more than thirty prostate cancer susceptibility variants. However these variants account for less than a third of familial risk of the disease. Epigenetic factors may prove key to understanding this ‘missing heredity link’ as it is becoming more evident that high-risk variants may occur in the regulatory regions of genes.
DNA methylation, the most commonly studied epigenetic mark, is frequently disrupted in disease, particularly cancer, where global demethylation occurs in conjunction with promoter specific hypermethylation. While many gene promoters have been found to be hypermethylated in prostate cancer and associated with transcriptional repression, the mechanism initiating this aberrant methylation is yet to be fully understood. By examining the methylation pattern of specific gene regions using Illumina’s Infinium HumanMethylation450 BeadChip platform we aim to identify additional high-risk variants with potential uses as biomarkers and treatment targets. Around 50 blood DNA samples from affected men from the Tasmanian Familial Prostate Cancer Resource together with unaffected relatives across three generations have been interrogated on the platform. Analysis of these methylation patterns will not only allow the investigation of disease associated aberrant marks, particularly in relation to SNPs, but also the exploration of transgenerational epigenetic inheritance.