Sex Differences in Cancer Genomes: Much Learned, More Unknown

Cancer is a leading cause of death worldwide. Sex influences cancer in a bewildering variety of ways. In some cancer types, it affects prevalence; in others, genomic profiles, response to treatment, or mortality. In some, sex seems to have little or no influence. How and when sex influences cancer initiation and progression remain a critical gap in our understanding of cancer, with direct relevance to precision medicine. Here, we note several factors that complicate our understanding of sex differences: representativeness of large cohorts, confounding with features such as ancestry, age, obesity, and variability in clinical presentation. We summarize the key resources available to study molecular sex differences and suggest some likely directions for improving our understanding of how patient sex influences cancer behavior.