Sex disparity in skin carcinogenesis and potential influence of sex hormones.

Background: Sex or gender disparity in skin cancer has been documented for a long time at the population level. UV radiation (UVR) is a common environmental risk for all three major types of skin cancer: cutaneous melanoma (CM), basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). The underlying mechanism for sex disparity has been largely attributed to sex-differentiated behaviour patterns related to UVR. Non-UVR factors such as intrinsic physiological differences have been suggested but remain understudied. Aims Materials and Methods: This review summarizes and compares the known sex differences in three skin cancer types with regard to body site distribution and age influence. Results: We found a similar age-dependent sex difference pattern in CM and BCC. Specifically, CM and BCC tend to show higher incidence in young women and old men, with a switching age around menopause. The switching age suggests involvement of sex hormones, which has shown controversial influence on skin cancers at epidemiological level. Literatures regarding sex hormone receptors for oestrogen, androgen and progesterone are summarized for potential explanations at molecular level. Discussion: Overall, more and more evidence suggests non-UVR factors such as sex hormones play critical roles in skin cancer (especially CM and BCC), yet solid population and molecular evidence are required. Incidences of skin cancer are increasing which suggests limited effect for the current UVR-avoidance prevention methods. Conclusion: Fully understanding the causes of sex disparities in incidence is necessary for developing a comprehensive prevention strategy.