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

Jue-Sheng Ong (), Mathias Seviiri, Jean Claude Dusingize, Yeda Wu, Xikun Han, Jianxin Shi, Catherine M. Olsen, Rachel E. Neale, John F. Thompson, Robyn P. M. Saw, Kerwin F. Shannon, Graham J. Mann, Nicholas G. Martin, Sarah E. Medland, Scott D. Gordon, Richard A. Scolyer, Georgina V. Long, Mark M. Iles, Maria Teresa Landi, David C. Whiteman, Stuart MacGregor and Matthew H. Law ()
Additional contact information
Jue-Sheng Ong: Population Health Department, QIMR Berghofer Medical Research Institute
Mathias Seviiri: Population Health Department, QIMR Berghofer Medical Research Institute
Jean Claude Dusingize: Population Health Department, QIMR Berghofer Medical Research Institute
Yeda Wu: Population Health Department, QIMR Berghofer Medical Research Institute
Xikun Han: Population Health Department, QIMR Berghofer Medical Research Institute
Jianxin Shi: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
Catherine M. Olsen: Population Health Department, QIMR Berghofer Medical Research Institute
Rachel E. Neale: Population Health Department, QIMR Berghofer Medical Research Institute
John F. Thompson: The University of Sydney
Robyn P. M. Saw: The University of Sydney
Kerwin F. Shannon: The University of Sydney
Graham J. Mann: The University of Sydney
Nicholas G. Martin: Department of Mental Health & Neuroscience, QIMR Berghofer Medical Research Institute
Sarah E. Medland: Department of Mental Health & Neuroscience, QIMR Berghofer Medical Research Institute
Scott D. Gordon: Department of Mental Health & Neuroscience, QIMR Berghofer Medical Research Institute
Richard A. Scolyer: The University of Sydney
Georgina V. Long: The University of Sydney
Mark M. Iles: University of Leeds
Maria Teresa Landi: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
David C. Whiteman: Population Health Department, QIMR Berghofer Medical Research Institute
Stuart MacGregor: Population Health Department, QIMR Berghofer Medical Research Institute
Matthew H. Law: Population Health Department, QIMR Berghofer Medical Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-41231-8

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