Understanding Nonmelanoma Skin Cancer

What Your Skin’s DNA Can Tell You About Your Risk For Skin Cancer

Apr 27, 2023

BY DERMTECH EDITORIAL TEAM

There are many reasons to love and appreciate the skin you’re in. And now there’s one more.

Our skin can tell us a lot about our overall health, making it critical to both protect and examine it regularly. Dermatologists often describe the skin as a “window” into the health of their patients.1 And that can be true for a variety of reasons. It’s quite common for symptoms of skin cancer and other conditions, like diabetes and lupus, to show up on the skin– usually through rashes and/or lesions.1 Early detection of these symptoms is key to having the most treatment options available.2

Within each skin cell lies an important component: DNA, which provides information about our health that may not be visible to the human eye. DNA from skin cells can be analyzed to determine the risk for a variety of diseases, including nonmelanoma skin cancer.

So what exactly is DNA from skin cells, and why is it important?

DNA is the chemical code that tells different cell types, including skin cells, how to grow and function.  

There are many different types of skin cells, each with a specific function. Some of the most important skin cells for skin health are basal cells, keratinocytes, melanocytes and Langerhans cells.3

Basal cells continuously divide and produce new skin cells. The new skin cells push up toward the surface of the skin as older skin cells are shed at the skin’s surface.3

Keratinocytes are the most common type of skin cell and have a primary function of protecting our skin from harmful environmental factors like UV rays and pollution.3,4 

Melanocytes are mainly responsible for producing melanin, the pigment that gives skin its color. Melanin also plays a significant role in protecting our skin from UV damage.3

Langerhans cells are immune cells that help to protect skin from both infection and diseases, making the cells an important part of our skin’s defense system.5

Research shows that UV radiation is one of the major environmental factors linked to DNA damage in skin cells.6 This damage is often caused by frequent exposure to both UVA and UVB rays from the sun or other manmade sources, like tanning beds, and is not always visible to the naked eye.

While our bodies can naturally repair some of the DNA damage in skin cells, it’s not always possible to repair all of it.6,7 DNA damage that goes unrepaired in skin cells can result in mutations (changes in the DNA code), some of which may cause cells to multiply excessively, which can lead to cancer.8,9

Scientists are researching how and if damage to skin DNA can be reversed or repaired. Currently, there are options to reduce the visual aspects of sun damage to the skin through topical treatments and procedures. Board-certified dermatologists may use and recommend retinoids, chemical peels, laser treatment and/or microdermabrasion.10

There are two main types of skin cancer: melanoma and nonmelanoma. While melanoma is a less common type of skin cancer, it is far more dangerous and deadly.11 Nonmelanoma skin cancer, on the other hand, is one of the most common types of cancer, with over 5.4 million cases of basal and squamous cell cancers diagnosed in the U.S. each year.12 Additionally, actinic keratosis (AK), or precancer, affects more than 40 million Americans and can also lead to nonmelanoma skin cancer if not detected and treated.13

Certain genes and mutations are also known to be associated with both nonmelanoma skin cancers and AKs. These include the TP53 and NOTCH1 genes. When these genes become damaged due to UV exposure, they become drivers of premalignant AKs and malignant nonmelanoma skin cancers.14,15,16  

Though research shows that catching cancer early typically allows for more treatment options, it is very possible for skin cancer symptoms to go unnoticed. In addition, there could be some DNA damage that goes undetected as it is not necessarily visible on the skin surface. While some patients are able to catch the early signs of nonmelanoma skin cancer through common symptoms, other patients may not notice any symptoms at all.17 This is why testing the DNA of your skin cells to check the health of your skin is so important. Identifying sun damaged skin early through regular skin checks can help you take steps to prevent skin cancer down the line. In the near future, there will be a way to detect damage to DNA markers that are associated with nonmelanoma skin cancer.

So, what next?

If you have skin cancer risk factors, such as a history of severe sunburns, older age, fair skin, a weakened immune system, and using tanning beds, testing the DNA your skin may be a good option for you.18,19,20 If you are at high risk for nonmelanoma skin cancer, your doctor may recommend regular skin exams to promote early detection.

Preventing skin cancer is important for your health. Taking the time to learn more about this disease and how to protect yourself is crucial. It is possible to enjoy the outdoors safely and still protect your skin. Taking the following precautions can help reduce your skin cancer risk:21

  • Seek shade, especially during midday hours when the sun’s rays are the strongest.22
  • Wear clothing that covers your skin, including a wide-brimmed hat, long-sleeved shirt and pants.24
  • Apply sunscreen with an SPF of 30 or higher, reapplying every two hours or after swimming or sweating.24
  • Avoid indoor tanning beds.22

While skin cancer is a serious disease, it is important to remember that it is highly treatable when detected early.23 With early detection and treatment, skin cancer is beatable. If you notice any changes to your skin, be sure to see your doctor right away.

  1. American Academy of Dermatology Association. What your skin can tell you about your overall health. https://www.aad.org/public/diseases/a-z/skin-overall-health. Accessed March 30, 2023.
  2. American Cancer Society. Early Detection, Diagnosis, and Staging. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/detection-diagnosis-staging.html. Accessed April 17, 2023
  3. National Cancer Institute. Layers of the skin. https://training.seer.cancer.gov/melanoma/anatomy/layers.html. Accessed March 30, 2023.
  4. Johansen C. Generation and Culturing of Primary Human Keratinocytes from Adult Skin. J Vis Exp. 2017 Dec 22;(130):56863.
  5. Clayton K, Vallejo A, Davies J, Sirvent S, Polak M. Langerhans cells – programmed by the epidermis. Front Immunol. 2017;11. doi:10.3389/fimmu.2017.01676
  6. Markiewicz E, Idowu OC. DNA damage in human skin and the capacities of natural compounds to modulate the bystander signaling. Open Biology. 2019;9(12). doi:10.1098/rsob.190208
  7. American Cancer Society. Ultraviolet (UV) Radiation. https://www.cancer.org/healthy/cancer-causes/radiation-exposure/uv-radiation.html. Accessed April 17, 2023.
  8. Gorbunova V, Seluanov A, Mao Z, Hine C. Changes in DNA repair during aging. Nucleic Acids Research. 2007;12.
  9. American Cancer Society. Oncogenes, tumor suppressor genes, and DNA repair genes. https://www.cancer.org/healthy/cancer-causes/genetics/genes-and-cancer/oncogenes-tumor-suppressor-genes.html. Accessed March 30, 2023.
  10. American Academy of Dermatology. How Dermatologists Treat Sun-Damaged Skin. https://www.aad.org/public/everyday-care/sun-protection/sun-damage-skin/wrinkles-sun-damage-can-be-treated.  Accessed April 17, 2023.
  11. American Academy of Dermatology. Skin cancer. https://www.aad.org/media/stats-skin-cancer. Accessed April 17, 2023.
  12. American Cancer Society. Key statistics for basal and squamous cell skin cancers. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/about/key-statistics.html. Accessed April 17, 2023.
  13. American Academy of Dermatology. Actinic keratosis: Overview. https://www.aad.org/public/diseases/skin-cancer/actinic-keratosis-overview. Accessed April 17, 2023.
  14. Chang D, Shain AH. The landscape of driver mutations in cutaneous squamous cell carcinoma. NPJ Genom Med. Jul 16, 2021;6(1):61. doi:10.1038/s41525-021-00226-4
  15. Bonilla X, Parmentier L, King B, et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nat Genet. Apr 2016;48(4):398-406. doi:10.1038/ng.3525
  16. Thomson J, Bewicke-Copley F, Anene CA, et al. The Genomic Landscape of Actinic Keratosis. J Invest Dermatol. Jul 2021;141(7):1664-1674 e7. doi:10.1016/j.jid.2020.12.024
  17. American Cancer Society. Signs and symptoms of basal and squamous cell skin cancers. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/detection-diagnosis-staging/signs-and-symptoms.html. Accessed April 4, 2023.
  18. Wu S, Cho E, Li W-Q, Weinstock MA, Han J, Qureshi AA. History of severe sunburn and risk of skin cancer among women and men in 2 prospective cohort studies. American Journal of Epidemiology. 2016;183(9):824-833. doi:10.1093/aje/kwv282
  19. American Cancer Society. Basal and squamous cell skin cancer risk factors. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/causes-risks-prevention/risk-factors.html#:~:text=in%20these%20areas.-,Smoking,factor%20for%20basal%20cell%20cancer. Accessed March 30, 2023.
  20. An S, Kim K, Moon S, et al. Indoor Tanning and the Risk of Overall and Early-Onset Melanoma and Nonmelanoma Skin Cancer: Systematic Review and Meta Analysis. Cancers (Basel). 2021;13(23):5940. Published 2021 Nov 25. doi:10.3390/cancers1323594 0
  21. National Cancer Institute. Skin cancer prevention (PDQ) – patient version. https://www.cancer.gov/types/skin/patient/skin-prevention-pdq. Accessed March 30, 2023.
  22. American Academy of Dermatology. Practice safe sun: how to practice safe sun. https://www.aad.org/public/everyday-care/sun-protection/shade-clothing-sunscreen/practice-safe-sun. Accessed March 30, 2023.
  23. American Academy of Dermatology. American Academy of Dermatology issues new guidelines for treatment of nonmelanoma skin cancer. https://www.aad.org/news/guidelines-to-treat-nonmelanoma-skin-cancer. Accessed Jan. 18, 2023.