A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma-Reference-Cited by-同舟云学术

A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma

Published:2022-12-10 Issue:1 Volume:13 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

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

Abstract

AbstractBasal 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.

Funder

Department of Health | National Health and Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-022-35345-8.pdf

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