Genetic risk factors for skin cancer: 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]

This article covers the three types of skin cancer, the genetic variants that increase your risk, and lifehacks for preventing skin cancer.

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 3 different types of skin cancer:

  • basal cell carcinoma
  • squamous cell carcinoma
  • melanoma

Basal Cell Carcinoma:

This is the most common type of skin cancer, and it rarely metastasizes. Basal cell carcinomas (BCCs) are easily removed, especially at the early stages, and it is the least deadly type. This type of skin cancer can be caused by sun exposure.

Squamous cell carcinoma:

Squamous cell carcinomas are the second most common type of skin cancer. It can be cured when caught early, but there is a risk of metastasis to the lymph nodes, so it needs to be taken care of quickly. 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 type of skin cancer because they can metastasize rapidly. They can arise from a mole (nevus) or from 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]

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) that are linked 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 who are 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 the production of 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, go get it checked out. The earlier skin cancer is detected, the more likely you will have a good outcome.

ABCD rule:

Wondering what ‘odd-looking’ means when it comes to a mole?  The ABCD rule can be used to determine 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:

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

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

Green tea polyphenols, such as EGCG, have 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 that is 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.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.