Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

It has been known for decades that cancer occurs differently in men and women. On average, men are more likely to be diagnosed with cancer than women -- even after adjusting for differences in lifestyle like smoking and occupation. Many tumour types show striking asymmetry in incidence rates: for example, thyroid cancer occurs ~2.5 times more frequently in women than men. Further, men and women often respond differently to therapy, with women often responding better to surgery and chemotherapy than men. Surprisingly, the origin of these differences remains largely unknown. One candidate explanation is that the mutagenic processes that damage DNA to cause cancer do so in different ways in men and women. We propose to exploit two recently-developed, large, multi-national dataset of tumour genome sequences. We will study 20 different cancer types, and for each specifically compare the mutations occurring in tumours of men and in tumours of women using statistical and computational techniques to understand if there are recurrent differences between them. To date, preliminary analyses suggest that there are substantial genetic differences in tumours between the sexes. This work has the potential to transform the way cancer is researched by placing increased focus on the sex of model systems used, as well as to greatly influence the application of targeted therapies which may be differentially effective between the sexes.