Is Skin Cancer Genetic? How to check your genetic raw data

Skin cancer is the most common type of cancer, and in the US, there are about 1 million cases of skin cancer diagnosed each year.[ref]

The three types of skin cancer, the genetic variants that enhance your risk, and skin cancer prevention tips are all covered in this article.

Skin Cancer Types, Genetics, and Risk Factors:

The Skin Cancer Foundation estimates that about 1 in 5 people in the US will get skin cancer by the age of 70.[ref] Other regions around the world vary in skin cancer risk based on sun exposure and the typical skin color of the population.

There are three different types of skin cancer:

  • basal cell carcinoma
  • squamous cell carcinoma
  • melanoma

Basal Cell Carcinoma:

The most frequent type of skin cancer is basal cell carcinoma (BBC), which seldom metastasizes. This form of skin cancer is the least deadly and is easily removed, especially in the early stages. Sun exposure can cause this type of skin cancer.

Squamous cell carcinoma:

Squamous cell carcinomas are the second most common type of skin cancer. It is curable if caught early, but there is a risk of metastasis to the lymph nodes, so it must be treated as soon as possible. These are often sun (or UV) induced cancers.

Malignant Melanoma:

Melanomas are dark, irregularly shaped skin cancers. These are the least common but most dangerous types of skin cancer because they can metastasize rapidly. They can arise from a mole (nevus) or a thickened patch of sun-damaged skin (solar elastosis).[ref]

Why does UV radiation cause skin cancer?

Cancer arises through DNA mutations in tumor suppressor genes or oncogenes. UV-B radiation can cause breaks in the nuclear DNA, and when the cells divide, this can cause a change (mutation) in a tumor suppressor or oncogene. Up to 95% of the time, skin cancer mutations include UV-radiation induced changes to the TP53 gene, which codes for a tumor suppressor.[ref]

What are the risk factors for skin cancer?

Genetic variants increase the risk of skin cancer (covered in detail below). But genes alone don’t cause skin cancer. Instead, it is the combination of genetic variants along with lifestyle and environmental risk factors for skin cancer.[ref]

Sun exposure: We need sun exposure on our skin to produce vitamin D, but this is a double-edged sword… the UV radiation from the sun also increases the risk of skin cancer. Avoid getting sunburned, and instead, be sure to cover up after getting a reasonable amount of sun exposure.

Age: As we age, the ability of the body to detect and fight off cancer decreases. Thus, like other cancers, the risk of skin cancer increases with age.

Fair skin: People with genetic variants (below) with links to fairer skin color are at an increased risk of skin cancer.

Immunosuppressants: Organ transplant patients are at a 100-fold increase in risk for squamous cell carcinoma.[ref] Immunosuppressants increase the risk for skin cancer due to viral agents such as HPV and herpes virus.[ref]

PAH exposure: People exposed to higher amounts of polycyclic aromatic hydrocarbons (PAHs) are at a higher risk for skin cancer. Occupations such as iron and steel production, roofing, road paving, chimney sweeping, and aluminum production can increase exposure to PAHs.[ref]

 


Genetic Variants that increase the risk of skin cancer:

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MC1R gene: The melanocortin 1 receptor (MC1R) is important in producing the pigment called melanin. Genetic variants in MC1R increase the risk for skin cancer — and they also are the reason for red hair.

Check your genetic data for rs1805008 (23andMe v4, v5; AncestryDNA):

  • T/T: red hair possible; increased risk of melanoma, BCC[ref][ref][ref][ref]
  • C/T: increased risk of melanoma, BCC
  • C/C: typical

Members: Your genotype for rs1805008 is .

Check your genetic data for rs1805007 (23andMe v4, v5; AncestryDNA):

  • T/T: red hair is likely; increased risk of melanoma, BCC[ref][ref]
  • C/T: higher risk of melanoma, BCC
  • C/C: typical

Members: Your genotype for rs1805007 is .

Check your genetic data for rs1805006 (23andMe v4):

  • A/A: red hair is likely; increased risk of melanoma, BCC[ref][ref]
  • A/C: higher risk of melanoma
  • C/C: typical

Members: Your genotype for rs1805006 is .

Check your genetic data for i3002507 or rs1805009 (23andMe v4, v5; AncestryDNA):

  • C/C: red hair possible, increased risk of melanoma[ref][ref]
  • C/G: higher risk of melanoma
  • G/G: typical

Members: Your genotype for rs1805009 is .

 

ASIP gene: agouti signaling protein, which causes melanocytes to synthesize blond hair instead of brown/black.

Check your genetic data for rs1015362 (23andMe v4, v5; AncestryDNA):

  • C/C: increased risk of skin cancer[ref] increased sun sensitivity (sunburns, freckles)[ref][ref]
  • C/T: increased sun sensitivity
  • T/T: not at increased risk of skin cancer

Members: Your genotype for rs1015362 is .

Check your genetic data for rs4911414 (23andMe v4, v5; AncestryDNA):

  • T/T: increased risk of skin cancer when combined with rs1015362 (above)[ref][ref] increased sun sensitivity (sunburns, freckles)[ref]
  • G/T: increased sun sensitivity (sunburns, freckles)
  • G/G: not at an increased risk of skin cancer

Members: Your genotype for rs4911414 is .

 

near EXOC2 gene: exocyst complex component 2

Check your genetic data for rs12210050 (23andMe v4, v5; AncestryDNA):

  • C/C: typical risk
  • C/T: slightly higher risk for skin cancer (BCC)
  • T/T: slightly higher risk for skin cancer (BCC)[ref][ref]

Members: Your genotype for rs12210050 is .

 

SLC45A2 gene: codes for a transporter protein important in melanin synthesis

Check your genetic data for rs16891982 (23andMe v4, v5; AncestryDNA):

  • C/C: (likely non-European ancestry) typical
  • C/G: For those with European ancestry, ~ 50% decreased risk of melanoma[ref]
  • G/G: typical risk for European ancestry

Members: Your genotype for rs16891982 is .

 

PADI6 gene: Peptidyl Arginine Deiminase 6

Check your genetic data for rs7538876 (23andMe v4, v5; AncestryDNA):

  • A/A: slightly increased risk of skin cancer (BCC)[ref]
  • A/G: normal risk of skin cancer
  • G/G: slightly decreased risk of skin cancer (BCC)

Members: Your genotype for rs7538876 is .

 

IRF4 gene: codes for an interferon regulatory factor that is important in response to viruses and the activation of the immune system.

Check your genetic data for rs12203592 (23andMe v4, v5; AncestryDNA):

  • T/T: increased risk of skin cancer[ref] increased risk of melanoma due to solar elastosis (not moles)[ref] increased sun sensitivity (sunburns, freckles)[ref] increased moles[ref]
  • C/T: increased sun sensitivity (sunburns, freckles), moles
  • C/C: most common genotype, not at an increased risk of skin cancer

Members: Your genotype for rs12203592 is .


Lifehacks:

If you have questions about an odd-looking skin patch, get it checked out. The earlier skin cancer is detected, the more likely you will have a good outcome.

ABCD skin cancer rule:

Do you wonder what ‘odd-looking’ means when it comes to a mole?  The ABCD rule for skin cancer determines if a mole or irregular dark spot is possibly a melanoma.

    • Asymmetry – the mole is asymmetric
  • Border irregularity – mole border is not smooth
  • Color – different colors in the pigmented area
  • Diameter – if the spot is larger than 6 mm in diameter

Supplements for cancer protection:

Nicotinamide, a form of vitamin B3, reduced the risk of skin cancer in randomized, controlled clinical trials.[ref][ref] Researchers theorize this is due to boosting NAD, a key enzyme needed for cellular energy and DNA repair.[ref]

Polypodium leucotomos is a species of fern used for photoprotection in people with skin sensitive to UV radiation.[ref]

Green tea polyphenols, such as EGCG, have been shown in numerous animal and cell studies to decrease UV-B-induced DNA changes.[ref]


Related Articles and Genes:

Vitamin D, Genes, and Your Immune System
Vitamin D is more than just a ‘vitamin’. It is actually a hormone essential to so many processes in your body – including your immune system.

Why light at night increases the risk for cancer
The World Health Organization listed ‘light at night’ as a possible carcinogen in 2007.  Let’s let that sink in for a minute… On the same list of possible carcinogens that includes formaldehyde, aflatoxin, and the HPV virus is something as innocent as artificial light at night.

ABCC11 gene: Ear wax and no body odor
The ABCC11 gene determines both the type of earwax a person has and whether they have no armpit or body odor.

Does eating meat put you at a higher risk for colon cancer?
People who carry certain genetic variants are at an increased risk for colon cancer, depending on their processed meat intake. You can check your genetic data to see if processed meat is likely to increase your colon cancer risk.

 

References:

Berman, Brian, et al. “Polypodium Leucotomos – An Overview of Basic Investigative Findings.” Journal of Drugs in Dermatology : JDD, vol. 15, no. 2, Feb. 2016, pp. 224–28. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189711/.

Binstock, M., et al. “Single-Nucleotide Polymorphisms in Pigment Genes and Nonmelanoma Skin Cancer Predisposition: A Systematic Review.” The British Journal of Dermatology, vol. 171, no. 4, Oct. 2014, pp. 713–21. PubMed, https://doi.org/10.1111/bjd.13283.

Boffetta, P., et al. “Cancer Risk from Occupational and Environmental Exposure to Polycyclic Aromatic Hydrocarbons.” Cancer Causes & Control: CCC, vol. 8, no. 3, May 1997, pp. 444–72. PubMed, https://doi.org/10.1023/a:1018465507029.

Chen, Andrew C., et al. “A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.” The New England Journal of Medicine, vol. 373, no. 17, Oct. 2015, pp. 1618–26. PubMed, https://doi.org/10.1056/NEJMoa1506197.

Corchado-Cobos, Roberto, et al. “Cutaneous Squamous Cell Carcinoma: From Biology to Therapy.” International Journal of Molecular Sciences, vol. 21, no. 8, Apr. 2020, p. 2956. PubMed Central, https://doi.org/10.3390/ijms21082956.

Denny, Joshua C., et al. “Systematic Comparison of Phenome-Wide Association Study of Electronic Medical Record Data and Genome-Wide Association Study Data.” Nature Biotechnology, vol. 31, no. 12, Dec. 2013, pp. 1102–10. PubMed Central, https://doi.org/10.1038/nbt.2749.

Gibbs, David C., et al. “Association of Interferon Regulatory Factor-4 Polymorphism Rs12203592 With Divergent Melanoma Pathways.” JNCI Journal of the National Cancer Institute, vol. 108, no. 7, Feb. 2016, p. djw004. PubMed Central, https://doi.org/10.1093/jnci/djw004.

Kvaskoff, Marina, et al. “Polymorphisms in Nevus-Associated Genes MTAP, PLA2G6, and IRF4 and the Risk of Invasive Cutaneous Melanoma.” Twin Research and Human Genetics: The Official Journal of the International Society for Twin Studies, vol. 14, no. 5, Oct. 2011, pp. 422–32. PubMed, https://doi.org/10.1375/twin.14.5.422.

Lindelöf, B., et al. “Incidence of Skin Cancer in 5356 Patients Following Organ Transplantation.” The British Journal of Dermatology, vol. 143, no. 3, Sept. 2000, pp. 513–19.

Maccioni, Livia, et al. “Variants at Chromosome 20 (ASIP Locus) and Melanoma Risk.” International Journal of Cancer, vol. 132, no. 1, Jan. 2013, pp. 42–54. PubMed, https://doi.org/10.1002/ijc.27648.

Moon, Debbie. “Genetics of Red Hair.” Genetic Lifehacks, 18 Apr. 2020, https://www.geneticlifehacks.com/the-redhead-gene/.

Morgan, Michael D., et al. “Genome-Wide Study of Hair Colour in UK Biobank Explains Most of the SNP Heritability.” Nature Communications, vol. 9, no. 1, Dec. 2018, p. 5271. PubMed, https://doi.org/10.1038/s41467-018-07691-z.

Nan, Hongmei, et al. “Genome-Wide Association Study Identifies Novel Alleles Associated with Risk of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma.” Human Molecular Genetics, vol. 20, no. 18, Sept. 2011, pp. 3718–24. PubMed, https://doi.org/10.1093/hmg/ddr287.

Nazarali, S., and P. Kuzel. “Vitamin B Derivative (Nicotinamide)Appears to Reduce Skin Cancer Risk.” Skin Therapy Letter, vol. 22, no. 5, Sept. 2017, pp. 1–4.

Scatozza, Francesca, et al. “Nicotinamide Inhibits Melanoma in Vitro and in Vivo.” Journal of Experimental & Clinical Cancer Research: CR, vol. 39, no. 1, Oct. 2020, p. 211. PubMed, https://doi.org/10.1186/s13046-020-01719-3.

Siewierska-Górska, A., et al. “Association of Five SNPs with Human Hair Colour in the Polish Population.” Homo: Internationale Zeitschrift Fur Die Vergleichende Forschung Am Menschen, vol. 68, no. 2, Mar. 2017, pp. 134–44. PubMed, https://doi.org/10.1016/j.jchb.2017.02.002.

Singh, Madhulika, et al. “New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.” BioMed Research International, vol. 2014, 2014, p. 243452. PubMed Central, https://doi.org/10.1155/2014/243452.

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Tagliabue, E., et al. “MC1R Gene Variants and Non-Melanoma Skin Cancer: A Pooled-Analysis from the M-SKIP Project.” British Journal of Cancer, vol. 113, no. 2, July 2015, pp. 354–63. PubMed, https://doi.org/10.1038/bjc.2015.231.

—. “MC1R Gene Variants and Non-Melanoma Skin Cancer: A Pooled-Analysis from the M-SKIP Project.” British Journal of Cancer, vol. 113, no. 2, July 2015, pp. 354–63. PubMed, https://doi.org/10.1038/bjc.2015.231.

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Zaorska, Katarzyna, et al. “Prediction of Skin Color, Tanning and Freckling from DNA in Polish Population: Linear Regression, Random Forest and Neural Network Approaches.” Human Genetics, vol. 138, no. 6, 2019, pp. 635–47. PubMed Central, https://doi.org/10.1007/s00439-019-02012-w.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.