Gender and sex differences in colorectal cancer screening, diagnosis and treatment

Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes. However, gender differences also play a role, affecting risk factors, access to or participation in screening and treatment, and patients' experience of treatment (e.g. adverse events and sequelae). Sex and gender issues warrant further investigation in CRC to optimise treatment outcomes for patients.