Uncovering the complex relationship between balding, testosterone and skin cancers in men

• Published in: Nature communications Vol. 14; no. 1; p. 5962
• Main Authors: Ong, Jue-Sheng, Seviiri, Mathias, Dusingize, Jean Claude, Wu, Yeda, Han, Xikun, Shi, Jianxin, Olsen, Catherine M., Neale, Rachel E., Thompson, John F., Saw, Robyn P. M., Shannon, Kerwin F., Mann, Graham J., Martin, Nicholas G., Medland, Sarah E., Gordon, Scott D., Scolyer, Richard A., Long, Georgina V., Iles, Mark M., Landi, Maria Teresa, Whiteman, David C., MacGregor, Stuart, Law, Matthew H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 692/308/174; 692/4028/67/1813/1349; 692/4028/67/1813/1352; 692/4028/67/1813/1634; 692/499; Androgens; Baldness; Cancer; Exposure; Genetic analysis; Head and neck carcinoma; Health risks; Humanities and Social Sciences; Melanoma; multidisciplinary; Nucleotides; Pathogenesis; Pigmentation; Scalp; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Skin cancer; Skin tests; Squamous cell carcinoma; Testosterone; Ultraviolet radiation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41231-8

Male-pattern baldness (MPB) is related 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. We dissected this relationship via Mendelian randomization (MR) analyses, using 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. We found strong associations between MPB and the risk of KC, 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. Men with less hair covering likely explains, at least in part, the higher incidence of melanoma in men residing in countries with high ambient UV. Male-pattern baldness (MPB) is related to dysregulation of androgens. Here, authors show that MPB (but not androgens) is associated with skin cancer risk, particularly in the scalp region, suggesting that sun exposure, rather than androgens, is the main driver.