Male-pattern baldness (MPB), also known as androgenetic alopecia, is characterised by progressive hair follicle miniaturisation, leading to hair loss in men and is often linked to dysregulation of androgens such as testosterone. A previously observed relationship between MPB and skin cancer may be due to greater exposure to ultraviolet radiation or indicate a role for androgenic pathways in the pathogenesis of skin cancers.

In the study published in Nature Communication, we examined to disentangle the complex (and potentially mediated) relationship between endogenous testosterone levels, MPB, and skin cancers through a series of univariable and multivariable Mendelian randomization (MVMR) analyses.

Authors used genetic data from recent male-only meta-analyses of cutaneous melanoma (12,232 cases; 20,566 controls) and keratinocyte cancers (KCs) (up to 17,512 cases; >100,000 controls), followed by stratified MR analysis by body-sites.

Strong associations between MPB and the risk of KC have been found, but not with androgens, and multivariable models revealed that this relationship was heavily confounded by MPB single nucleotide polymorphisms involved in pigmentation pathways. Site-stratified MR analyses revealed strong associations between MPB with head and neck squamous cell carcinoma and melanoma, suggesting that sun exposure on the scalp, rather than androgens, is the main driver.

In conclusion, genetic evidence in this study provides minimal support to the androgen-driven hypothesis linking sex hormones to the development of melanoma and keratinocyte cancers. Pigmentation-related factors very likely mediate the genetic relationship between balding and KCs at all body sites, evident through MVMR findings. Finally,a modest body-site specific association between MPB was observed and both the risk of melanoma and KCs involving the head and neck region greater than other body sites, suggesting that balding might increase susceptibility for melanoma around the head and neck region through reduced hair covering, a potential explanation for sex-differences in head and neck melanoma risk between men and women.