Male Sex is an Inherent Risk Factor for Basal Cell Carcinoma

Basal cell carcinoma (BCC) is more frequent among females <40 years old; however, it affects preferentially older males (>60 years old). In order to contribute to the study of the still largely unknown mechanisms that underlie this peculiar sex-dependent shift, we compared the kinetics of the increase of the age-specific BCC incidence rates (R) as a function of age in males and females. Studies reporting sex-stratified R were found using a PubMed search and male to female age-specific incidence rate ratios (RR) were calculated for each age-class as reported in each study and assigned to the mean of the corresponding age periods. Trends in age were assessed with Kendall's τ test and relationships between two variables by inverse variance method-weighed Loess and linear regression analysis. Sixteen data sets were eligible and confirmed a significant shift in the male to female ratio (Kendall's τ = 0.530; P < 0.001). Moreover, the slope parameter b = 1.205 (SE = 0.014) of the best fit (r2 = 0.980) regression line resulting by plotting male vs. female age-specific incidence rates predicts a statistically significant (P = 0.001), constant, about 20% faster increase of R in males of all ages. Similar relationship are also evident for cutaneous squamous cell and Merkel cell carcinoma and, even more intriguing, for sums of all cancers (excluding BCC and SCC) in many different registries. In conclusion, females are probably born with an inherently higher risk to develop BCC; however, also with a much slower increase rate of this risk as a function of age. Notably this observation seems to be not a BCC peculiarity. Because of its high incidence coupled with moderate morbidity and extremely low mortality rates, BCC may serve as a valuable, single-tumor paradigm to reproach the complex mechanisms that underline the interaction of age and sex in the pathogenesis of human malignancies.