Unravelling the genetics of testicular cancer (360G-Wellcome-202539_Z_16_Z)

Genome wide association studies (GWAS) have enabled great progress in our understanding of testicular germ cell tumour (TGCT), with 25 risk variants identified to date which increase cancer risk. Mapping a risk variant to its gene target is a non-trivial task, given the complex nature of gene regulation and possibility of long range regulatory effects. A systems level approach is required, with multiple regulatory data-sets combined to gain an integrated functional viewpoint. To this end, we propose using GWAS region fine-mapping, expression quantitative trait loci analysis and transcription factor binding analyses. The clinical benefits of this are two-fold. Firstly, there is potential for diagnostic utility, in particular testing healthy individuals to identify those at high risk. These individuals could then benefit from enhanced screening protocols with the ultimate aim of early detection/cancer prevention. Secondly these genetic variants offer rich biological insight into the mechanisms of cancer development, providing new opportunities for drug development. This second benefit is rapidly becoming a major focus, as genetic evidence is becoming increasingly important for drug target identification and validation.