Summary

Basal cell carcinoma is a malignant tumor that arises in the lower portion of the skin. It grows very slowly and almost never metastasizes, which defines its great prognosis. It usually arises in areas often exposed to the sun and appears as a shiny skin-colored, red or darker lesion.

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Observed genes

Polygenic score

Influential genes: TP53,MC1R, SLC45A2

In BCC, TP53 mutations are one of the most common genetic changes and can lead to the development and progression of the disease.

Some of the MC1R variants may increase the risk of BCC. The risk is thought to be related to the gene's role in skin pigmentation and response to UV radiation.

The SLC45A2 gene is involved in pigmentation, and its variants have been associated with skin color and susceptibility to skin cancer.

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Overview

Basal cell carcinoma, or BCC, is the most common cancer worldwide. It usually occurs on sun-exposed areas of your skin and can have various clinical presentations. The most important risk factor is sunlight exposure, others include age, personal and family history of BCC, immunosuppression, radiation therapy, arsenic exposure, etc. The definitive diagnosis can be made only after a biopsy. There are many treatment options available including surgery, topical medications, cryotherapy, laser therapy, etc. You can try preventing basal cell carcinoma development by avoiding the sun at peak hours and using sunscreen. BCC has an excellent prognosis when diagnosed and treated early. 

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Prevalence and Risk factors

Basal cell carcinoma is the most common cancer worldwide. In Europe, the estimated incidence is about 50 to 80 new patients per 100 000 persons per year.[1] Globally in 2019, there were 4 million cases. However, the incidence varies significantly across different countries and ages. 

The main risk factor of BCC is sunlight exposure - particularly the exposure to harmful UV rays, including tanning beds. The damage you get from UV rays depends on several factors, like the overall lifetime exposure, intensity, and skin type. You are much more exposed to the sun if you live in a sunny or high-altitude location. 

People with light skin that is easily freckled or sunburnt have a much higher rate of BCC development. 

However, 20% of BCC arise in areas that aren't sun-exposed, so other risk factors also play a role.[2] 

These include:

• Personal or family history of skin cancer. If you had BCC once or more, you would likely develop it again. 
• Increasing age
• Radiation therapy (for treatment of acne and other skin conditions) 
• Arsenic exposure. Arsenic is a toxic metal that increases the risk of several cancers, including BCC. It is widely found in the environment. However, most people have minimal exposure to it. 
• Immunosuppression. Immunosuppressive drugs, like antirejection medicine after transplant or meds to treat some autoimmune diseases, lower your body's ability to fight off cancer and significantly increase the risk of developing BCC. 
• Specific rare genetic syndromes, like xeroderma pigmentosum and nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome), put affected individuals at high risk for BCC development. 

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Genetics

Basal Cell Carcinoma (BCC) usually develops sporadically but it can also be a result of Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome), which is an autosomal dominant hereditary disorder (only one mutated allele can cause the disease). The key cause is considered to be the exposure to ultraviolet (UV) radiation, resulting in point mutations (usually represented by the C>T and CC>TT base transitions). BCC is known for its highest mutation rate among cancers, with over 65 mutations/Mbp (megabase pair). The genetic basis of sporadic BCC in the general population is still not fully uncovered. 

Some tumor suppressor genes and proto-oncogenes (mutation of this gene leads to uncontrolled cell division) have been involved in BCC development, PTCH1 and SMO genes, the TP53 tumor suppressor gene, and also the members of the RAS proto-oncogene family.[3]

Often, those changes lead to loss-of-function mutations in the PTCH1 gene or activating mutations in the SMO gene. Whole-exome sequencing (WES) analyses have also discovered different affected genes and pathways, including MYCN, PPP6C, PTPN14, STK19, and LATS1 genes.[4-6]

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Here in Macromo, polygenic risk scores are used to determine one's genetic risk. The polygenic risk score (PRS) is an estimate of the probability that an individual carries a given trait based on genetics, without considering environmental factors. Variants across their genome are summed and weighted according to their effect on the disease or trait.[7]

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Signs and symptoms

Basal cell carcinoma is usually found on sun-exposed areas, especially the face, ears, neck, scalp, chest, shoulders, and back. However, remember that it can also occur anywhere in the body, for example, on genitalia. 

Five warning signs can suggest it is BCC:

1. An open sore that does not heal. The ulcer can bleed, ooze or crust. The sore might persist for weeks or appear to recover and then come back.
2. A reddish or irritated area that may crust, itch, hurt or cause no discomfort.
3. A shiny bump or nodule that is pearly or clear, pink, red or white, or even tan, brown, or black. 
4. A small pink growth with a slightly raised, rolled edge and a crusted center. It may develop tiny vessels close to the surface over time. 
5. A scar-like area that is flat white, yellow, or waxy in color with poorly defined borders. It can be a warning sign of an invasive BCC.[8]

However, basal cell carcinoma can look different than the above-described presentations. Sometimes it can resemble some non-cancerous skin conditions like psoriasis or eczema. 

In people of color, the lesion can often be mistaken for moles since half of the lesions are brown.

Furthermore, basal cell carcinoma has a really low metastasizing potential, meaning it rarely spreads throughout the body. If you notice a suspicious lesion, you should consult your general practitioner or dermatologist.

Diagnosis

An experienced doctor can make a diagnosis based on the clinical manifestation alone. The dermatologist can use a dermatoscope, a special visual aid device for skin conditions. 

The definitive diagnosis is made upon a biopsy of the affected skin area. The doctor can take a small piece of tissue that will be examined under a microscope. In most cases a microscopic examination can be made after a full excision of the lesion. 

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Therapy 

Basal cell carcinoma is easily cured at its early stages. It's essential to treat it, so it doesn't lead to severe disfiguring complications. 

There are several treatment options available:

• Surgical removal is the preferred treatment for BCC, especially for lesions found in the early stages. There are various ways by which your dermatologist can perform the surgical removal, like excision, curettage (scraping the lesion off), or electrodesiccation (usage of electric current to remove the tumor). 
• Cryotherapy 
• Photodynamic (light) therapy 
• Laser therapy
• Topical medication 
• Radiation therapy

Basal cell carcinoma might need additional treatment if cancer has spread throughout the body.[9]

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Prevention 

Although BCC is the most common cancer worldwide, most cases are preventable. 

You can take several precautions to minimize the risk of skin cancer development.[10]

• Avoid sun exposure from 10 am to 4 pm. 
• Avoid tanning beds. 
• Use sunscreen with SPF 30 or higher daily, even on cloudy days. 
• Use special protective clothing. 
• Taking oral supplements of niacinamide (vitamin B3) can reduce the rate of development of skin cancer by 23% in individuals at high risk of BCC.[11]
• Check your skin regularly and note any changes and warning signs.
• Visit your dermatologist annually. 

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Prognosis

BCC's prognosis depends on its potential risk of recurrence, which is related to the location, and clinical and histopathological (microscopic) findings. 

Fortunately, most of the cases have an excellent prognosis. 

If left untreated for a long time, basal cell carcinoma can grow and become disfiguring and dangerous. Rarely can it spread deep into the tissue and bone or even to distant organs. 

If you once had BCC, it puts you at a higher risk of recurrence of this cancer and the development of another skin cancer, for example, melanoma. You should attend regular check ups to identify any new lesion as early as possible.

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Recommendations

• Avoid sun exposure from 10 am to 4 pm. 
• Avoid tanning beds. 
• Use sunscreen every day with an SPF of 30 or higher.
• Take oral supplements of niacinamide (vitamin B3).
• Check your skin regularly.
• Visit your dermatologist annually.

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