Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 May 21;5(10):e134783.
doi: 10.1172/jci.insight.134783.

Genetic and environmental factors underlying keratinocyte carcinoma risk

Hélène Choquet  1 , Sepideh Ashrafzadeh  2   3 , Yuhree Kim  2   3 , Maryam M Asgari  2   3 , Eric Jorgenson  1
Affiliations
Review

Genetic and environmental factors underlying keratinocyte carcinoma risk

Hélène Choquet et al. JCI Insight. .

Abstract

Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This Review summarizes the genomic regions associated with SCC and BCC risk, examines the genetic overlap between SCC and BCC, and discusses biological pathways involved in SCC and BCC development. Next, we review environmental factors that are associated with KC risk, including those that are shared between SCC and BCC as well as others that associated with only one type of KC. We conclude with a critical appraisal of current research and potential directions for future research.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: MMA has received grant funding to her institution from Pfizer.

Figures

Figure 1
Figure 1. Normal skin structure and keratinocyte carcinomas.
(A) Normal skin architecture showing composition of the dermis and epidermis (magnification 10×). The epidermis contains keratinocytes, which give rise to (B) squamous cell carcinoma (magnification 40×) and (C) basal cell carcinoma (magnification 40×). Images of SCC and BCC were taken from the National Cancer Institute (https://www.cancer.gov). Illustrated by Rachel Davidowitz.
Figure 2
Figure 2. Venn diagram of KC genetic factors.
While squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) have several independent risk factors, both share a subset of associated genetic loci. GWAS-identified genetic loci (black) associated at a genome-wide level of significance (P < 5.0 × 10-8) with SCC, BCC, or both. Inherited disorders genes (green). Genetic loci identified in both GWAS and inherited disorders (red). Genetic loci are order alphabetically. Illustrated by Rachel Davidowitz.
Figure 3
Figure 3. Venn diagram of environmental risk factors and protective factors for KCs.
This diagram illustrates associations noted in the literature between environmental factors and KC risk, not necessarily causal relationships. Protective (green) and risk factors (red) are shown. Illustrated by Rachel Davidowitz.
See this image and copyright information in PMC

References

    1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol. 2015;151(10):1081–1086. doi: 10.1001/jamadermatol.2015.1187. - DOI - PubMed
    1. Nehal KS, Bichakjian CK. Update on keratinocyte carcinomas. N Engl J Med. 2018;379(4):363–374. doi: 10.1056/NEJMra1708701. - DOI - PubMed
    1. Thieu K, Ruiz ME, Owens DM. Cells of origin and tumor-initiating cells for nonmelanoma skin cancers. Cancer Lett. 2013;338(1):82–88. doi: 10.1016/j.canlet.2012.05.008. - DOI - PMC - PubMed
    1. Zanetti R, et al. The multicentre south European study ‘Helios’. I: Skin characteristics and sunburns in basal cell and squamous cell carcinomas of the skin. Br J Cancer. 1996;73(11):1440–1446. doi: 10.1038/bjc.1996.274. - DOI - PMC - PubMed
    1. [No authors listed]. Skin Cancer Facts & Statistics. Skin Cancer Foundation. https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/ Updated April 16, 2020. Accessed April 23, 2020.

Publication types

MeSH terms