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

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 themaindriver.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.

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Item Type:	Article
Authors/Creators:	Ong, J.-S. https://orcid.org/0000-0002-6062-710X Seviiri, M. Dusingize, J.C. Wu, Y. https://orcid.org/0000-0002-5977-1526 Han, X. https://orcid.org/0000-0002-3823-7308 Shi, J. https://orcid.org/0000-0001-8606-4707 Olsen, C.M. https://orcid.org/0000-0003-4483-1888 Neale, R.E. Thompson, J.F. https://orcid.org/0000-0002-2816-2496 Saw, R.P.M. Shannon, K.F. https://orcid.org/0000-0001-8538-3132 Mann, G.J. https://orcid.org/0000-0003-1301-405X Martin, N.G. https://orcid.org/0000-0003-4069-8020 Medland, S.E. https://orcid.org/0000-0003-1382-380X Gordon, S.D. https://orcid.org/0000-0001-7623-328X Scolyer, R.A. https://orcid.org/0000-0002-8991-0013 Long, G.V. https://orcid.org/0000-0001-8894-3545 Iles, M.M. https://orcid.org/0000-0002-2603-6509 Landi, M.T. https://orcid.org/0000-0003-4507-329X Whiteman, D.C. https://orcid.org/0000-0003-2563-9559 MacGregor, S. https://orcid.org/0000-0001-6731-8142 Law, M.H. https://orcid.org/0000-0002-4303-8821
Copyright, Publisher and Additional Information:	© The Author(s) 2023 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
Keywords:	Humans; Melanoma; Skin Neoplasms; Alopecia; Testosterone; Androgens; Ultraviolet Rays; Male
Dates:	Published: 3 October 2023 Published (online): 3 October 2023 Accepted: 24 August 2023
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Pathology and Data Analytics
Depositing User:	Symplectic Publications
Date Deposited:	10 Sep 2024 11:20
Last Modified:	10 Sep 2024 11:20
Published Version:	http://dx.doi.org/10.1038/s41467-023-41231-8
Status:	Published
Publisher:	Springer Science and Business Media LLC
Identification Number:	10.1038/s41467-023-41231-8
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:204986

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

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