Is Basal Cell Carcinoma Hereditary? Genetic Risk Factors

If you’re diagnosed with basal cell carcinoma (BCC), you may wonder if genetics played a role. In most cases, exposure to ultraviolet (UV) light from the sun is the likely cause. UV light can damage DNA in skin cells, which may lead to tumor growth.

However, some people have genetic factors that raise their risk as well. Hereditary conditions passed down through families can cause BCC — but they’re less common. Those with fair skin, lighter eyes, and red hair have gene variants predisposing them to BCC.

This article will dive into the genetic and environmental risk factors associated with BCC. We’ll cover inherited syndromes that play a role and how genetic testing can help you prepare for a potential diagnosis.

How Do Genetics and Environment Affect Basal Cell Carcinoma Risk?

Your environment plays a large role in your risk for BCC. The main risk factor for all skin cancers is sun exposure. This includes melanoma and squamous cell carcinoma (SCC).

UV light from the sun can damage DNA in skin cells. If genes that help repair DNA develop mutations (changes), they may not be able to fix the damage.

Certain physical traits can also raise your risk of BCC. You should take extra steps to protect yourself from the sun if you have:

• Fair skin, which raises your risk of sunburns
• Freckles on skin that’s exposed to the sun
• Green or blue eyes
• Red or blond hair
• A tendency to burn rather than tan

Overall, people of European descent have a 30 percent chance of developing BCC in their lifetime.

The Role of Family History in Basal Cell Carcinoma

People with a family history of skin cancer are more likely to develop it themselves. For example, your chances of BCC rise if a first-degree relative has this cancer. First-degree relatives include your parents and siblings.

According to the National Cancer Institute, you’re 31 percent more likely to develop BCC if a parent or sibling also has it. A family history of other types of skin cancer also raises your risk of BCC.

Family history is one small piece of your skin cancer risk. It doesn’t guarantee you’ll develop it yourself.

The MC1R Gene and Basal Cell Carcinoma

People with changes in certain genes have a higher risk of BCC. The MC1R gene makes the melanocortin 1 receptor. This protein controls your skin pigmentation.

Melanin is the pigment that creates your eye, skin, and hair color. Specialized cells called melanocytes make melanin. Your body makes two types of melanin:

• Eumelanin — Causes darker hair and skin, and protects against UV light
• Pheomelanin — Causes lighter hair and skin, and doesn’t protect against UV light

Changes in the M1CR gene lead to more pheomelanin production. This means your skin is more sensitive to damage from sunlight. People with fair skin, freckles, and red hair typically have more pheomelanin.

What Hereditary Conditions Raise the Risk of Basal Cell Carcinoma?

Genetic conditions passed down through families can also cause BCC. The type of genetic condition affects your chances of developing skin cancer.

Gorlin Syndrome

Gorlin syndrome is a genetic condition that causes BCC. You may hear Gorlin syndrome called other names, such as:

• Nevoid basal cell carcinoma syndrome
• Basal cell nevus syndrome (BCNS)
• Gorlin-Goltz syndrome

Gorlin syndrome affects fewer than 50,000 people in the U.S. It’s caused by variations in genes that stop cancer growth, called tumor suppressor genes (TSGs).

Changes in the PTCH1, PTCH2, and SUFU genes can cause Gorlin syndrome. PTCH1 is the most common gene involved. Variations in these TSGs lead to uncontrolled cell growth, which creates tumors.

Gorlin syndrome is an autosomal dominant genetic condition. Everyone gets two copies of every gene — one from each parent. You only need to inherit one copy of a gene variant to develop Gorlin syndrome.

However, researchers think that you also need changes in the healthy copy of the TSG to get BCC. UV light from the sun can mutate the healthy TSG. This means that both copies of the gene can’t prevent cancer anymore.

The symptoms of Gorlin syndrome vary from person to person. Examples include:

• BCC on skin that’s exposed to the sun, like your neck, face, back, and chest
• Small pits or dents on your palms and the bottoms of your feet
• Noncancerous (benign) growths in your jawbone
• Abnormalities in your rib and spine bones
• An enlarged skull and forehead

Some people with Gorlin syndrome develop BCC as teenagers and young adults. Others never develop any skin cancer in their lifetime. Having fair skin raises your risk more than having dark-colored skin.

Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare genetic condition that makes your skin extremely sensitive to any UV light. The light can come from the sun or certain types of light bulbs.

Overall, people with XP are 10,000 times as likely to get skin cancer, including BCC. For about half of people with XP, skin cancer develops by age 9.

XP is caused by changes in DNA repair genes. When the sun damages DNA, proteins normally fix it to prevent cancer. However, people with XP can’t fix their DNA, which increases the risk of BCC.

Parents pass XP on to their children as an autosomal recessive disease. This means both parents need to pass down gene variants to cause XP.

Some people are carriers. This means they have one healthy copy and one variant copy of the gene. XP carriers usually don’t have any signs or symptoms of the condition. Two parents who are carriers for XP have a 25 percent chance of having a child with XP.

Signs and symptoms of XP include:

• Freckling on sun-exposed skin in toddlers, usually by age 2
• Blisters and burns that quickly form with sun exposure (less than 10 minutes in some cases)
• Dry, thinning skin
• Areas of very dark or light skin
• Visible small red blood vessels underneath the skin

Bazex-Dupré-Christol Syndrome

Bazex-Dupré-Christol syndrome (BDCS) is an extremely rare genetic skin disorder that causes BCC. Around half of people with BDCS develop BCC before their 20s.

Along with skin cancer, BDCS also causes:

• Dry skin
• Small, white bumps on the face (milia)
• Dark patches on the skin
• Less hair on the scalp and body
• Scars on the face, hands, elbows, and feet
• Sweating less than normal

BDCS is an X-linked dominant genetic disorder that affects the ACTRT1 gene. ACTRT1 is a TSG — when the gene changes, cancer cells can easily grow and form tumors.

X-linked diseases are passed down on the X chromosome. BDCS is a dominant genetic condition. This means you only need one mutated variant of the ACTRT1 gene to develop it.

Females have two X chromosomes, and males have one X and one Y chromosome. Mothers with BDCS have a 50 percent chance of passing the condition on to a child.

Males with the condition have a 100 percent chance of passing it to their daughters. This is because they only have one X chromosome to give them.

How Can You Learn More About Your Basal Cell Carcinoma Risk?

We know that UV light from the sun is the largest risk factor for BCC. The most important steps you can take to prevent skin cancer are:

• Wearing sunscreen, a hat, and a shirt when outside
• Finding shade under an umbrella, tree, or a building whenever possible
• Limiting your time outside at peak hours of sunlight, usually between 10 a.m. and 4 p.m.
• Avoiding tanning beds, which use UV light
• Doing regular skin checks for any suspicious moles or other skin lesions

If you have a strong family history of BCC or other skin cancer, be sure to tell your doctor. They may suggest genetic testing to look for variants that may be linked to hereditary conditions.

You may also need a referral to a genetic counselor. These specialists help people navigate new diagnoses and learn more about testing and treatments.

For example, certain tests can look for variants that cause BCNS. Knowing your genetic risk can help you plan for a potential diagnosis. If you have children, you can also learn about their risk for BCC.

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