Abstract

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers and have genetic overlap. Here, the authors use a multi-trait genetic and phenotypic analysis to reveal susceptibility loci for BCC and SCC, and report an optimised polygenic risk score for risk stratification.

Details

Title
A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
Author
Seviiri, Mathias 1   VIAFID ORCID Logo  ; Law, Matthew H. 2   VIAFID ORCID Logo  ; Ong, Jue-Sheng 3   VIAFID ORCID Logo  ; Gharahkhani, Puya 3   VIAFID ORCID Logo  ; Fontanillas, Pierre 4   VIAFID ORCID Logo  ; Aslibekyan, Stella 4 ; Auton, Adam 4 ; Babalola, Elizabeth 4 ; Bell, Robert K. 4 ; Bielenberg, Jessica 4 ; Bryc, Katarzyna 4 ; Bullis, Emily 4 ; Coker, Daniella 4 ; Partida, Gabriel Cuellar 4 ; Dhamija, Devika 4 ; Das, Sayantan 4 ; Elson, Sarah L. 4 ; Filshtein, Teresa 4 ; Fletez-Brant, Kipper 4 ; Freyman, Will 4 ; Gandhi, Pooja M. 4 ; Heilbron, Karl 4 ; Hicks, Barry 4 ; Hinds, David A. 4 ; Jewett, Ethan M. 4 ; Jiang, Yunxuan 4 ; Kukar, Katelyn 4 ; Lin, Keng-Han 4 ; Lowe, Maya 4 ; McCreight, Jey 4 ; McIntyre, Matthew H. 4 ; Micheletti, Steven J. 4 ; Moreno, Meghan E. 4 ; Mountain, Joanna L. 4 ; Nandakumar, Priyanka 4 ; Noblin, Elizabeth S. 4 ; O’Connell, Jared 4 ; Petrakovitz, Aaron A. 4 ; Poznik, G. David 4 ; Schumacher, Morgan 4 ; Shastri, Anjali J. 4 ; Shelton, Janie F. 4 ; Shi, Jingchunzi 4 ; Shringarpure, Suyash 4 ; Tran, Vinh 4 ; Tung, Joyce Y. 4 ; Wang, Xin 4 ; Wang, Wei 4 ; Weldon, Catherine H. 4 ; Wilton, Peter 4 ; Hernandez, Alejandro 4 ; Wong, Corinna 4 ; Tchakouté, Christophe Toukam 4 ; Olsen, Catherine M. 5   VIAFID ORCID Logo  ; Whiteman, David C. 6   VIAFID ORCID Logo  ; MacGregor, Stuart 2   VIAFID ORCID Logo 

1  QIMR Berghofer Medical Research Institute, Statistical Genetics Lab, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Queensland University of Technology, School of Biomedical Sciences, Faculty of Health, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953); Queensland University of Technology, Center for Genomics and Personalised Health, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
2  QIMR Berghofer Medical Research Institute, Statistical Genetics Lab, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Queensland University of Technology, School of Biomedical Sciences, Faculty of Health, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
3  QIMR Berghofer Medical Research Institute, Statistical Genetics Lab, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
4  23andMe, Inc, Sunnyvale, USA (GRID:grid.420283.f) (ISNI:0000 0004 0626 0858) 
5  QIMR Berghofer Medical Research Institute, Cancer Control Group, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
6  University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-35345-8
ProQuest document ID
2748910043
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.