Understanding the diversity of skin cancers

introduction
Melanomas
Basal cell carcinoma
Squamous cell carcinoma
Differences in skin cancer diagnosis by race and ethnicity
The cellular origin of skin cancer
Genetic differences in skin cancer
References
Further reading


introduction

Skin cancers occur in all skin types. There are several varieties of skin cancer, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma.

The incidence of skin cancer is steadily increasing worldwide, and mortality from this disease more than doubled in the decade from 1990 to 2010. Skin cancer is the leading cause of cancer globally, outnumbering the sum of all other tumors.

Reasons for this rising trend may include increased UV exposure, other environmental factors, genetic risk factors, improved surveillance programs, and earlier diagnoses.

Image Credit: Delevely Pics/Shutterstock.com

Image Credit: Delevely Pics/Shutterstock.com

Melanin is responsible for skin color. This pigment forms in melanocytes in the skin, which are larger and produce more pigment in people of color (POC).

Melanin is packaged in melanosomes, sacs of pigment, which are transferred to keratinocytes. In POC, they are evenly scattered throughout keratinocytes but aggregated within cells in whites.

The sun protection factor offered by cutaneous melanin in blacks is about 13, against only 3 in whites, due to the better absorption and deflection of ultraviolet (UV) rays falling on the skin. It is estimated that melanin in POCs filters twice as much UV light as skin in whites.

For this reason, whites are more commonly affected by skin cancer, especially melanomas. While melanin protects vulnerable immature skin cells from ultraviolet (UV)-induced DNA damage, which can induce cancerous changes, this protection is not absolute.

UV light can still induce photodamage in darker skin, leading to skin cancer. Additionally, a darker skin tone in POC can make recognition of the disease more difficult, leading to delayed diagnosis and poorer outcome.

Melanomas

Melanomas are the third most common type of skin cancer. They make up less than one percent of skin cancers, but are the cause of the majority of skin cancer-related deaths. They are three times more likely to be diagnosed late in the natural history of the disease than whites.

Thus, advanced melanoma is diagnosed in more than half of black patients and more than a quarter of Hispanic patients, compared to only 16% of whites. Five-year melanoma survival rates are 70% in black patients versus 94% for whites.

This is despite the fact that blacks and Hispanics have melanoma incidence rates about 20 and 5 times lower than those among whites, at 1, ~5, and ~22 per 100,000 individuals, respectively.

Melanomas in POC are often acral lentiginous melanomas (ALM). These occur mainly on the palms of the hands, soles of the feet, under the nail bed and in the nail. Up to 40% of cases are present on the sole of the foot.

These are typically not areas that get much sun exposure. By comparison, superficial spreading melanoma is the most common type in Hispanics and whites.

Among POCs, the Japanese have twice the incidence of melanomas, at 2.2 per 100,000, as other Asian races, with rates of 0.2 and 0.5 in Asian Indians and Chinese, respectively.

Basal cell carcinoma

The BCC is linked to exposure to UV rays and is, therefore, almost always present on the parts of the body exposed to the sun. The face is, therefore, a frequent site of onset in POC, with nine out of ten cases involving the head and neck.

BCC is numerically the leading skin cancer in whites and ranks second in POC. It includes nearly three out of four skin cancers in whites, but less than one out of three among POCs. BCC mainly occurs among POCs living in sunnier regions, most common among Latinos, Chinese, and Japanese, who have relatively lighter skin than other POCs.

Squamous cell carcinoma

SCC is related to lifelong sun exposure, especially in women. It is a rapidly growing skin cancer, commonly from a scar or pre-existing burns. SCC is the most common skin cancer in Black Americans and Asian Indians, but ranks second among Hispanics, Chinese, and Japanese Asians, among whom BCC leads.

Inflammation is the major risk factor for the development of SCC in POC. In black Americans, SCC occurs on the buttocks, hips, legs, and feet as a result of leprosy, non-healing ulcers, and other wound-healing conditions. In Asians, SCC also occurs in areas not exposed to the sun. However, UV light is expected to play a role in lighter skinned POC.

Differences in skin cancer diagnosis by race and ethnicity

Skin cancers in POC often occur in less visible or unexpected places, such as ALMs, which make up 8% of melanomas in Asian Americans. Immunosuppression, trauma, the presence of nevi, prior radiation therapy, and albinism are all present risk factors for melanoma in POC.

Skin cancer and black skin

Many clinical trials lack representative POC numbers, so the true incidence of skin cancer in these patients may not be known. Medical textbooks often do not show what POC skin cancers look like, making it more difficult for doctors and other health care professionals to recognize these conditions.

Again, POCs are incorrectly assumed to be at low risk for skin cancer and are typically not warned to look out for signs of this disease or advised about preventative measures and their critical importance.

POCs often have fewer health facilities in terms of proximity or opening hours. They may not be covered by adequate health insurance.

Finally, many cases occur in relatively underdeveloped regions of the world, where cost and logistical considerations rule out all but basic cancer treatment. Little or no cancer screening facilities mean many cases are missed.

POC can represent the majority of the US population within a decade or two, underlining the need to study skin cancers in minority populations and create awareness about them and develop guidelines for prevention, diagnosis and treatment.

The cellular origin of skin cancer

The BCC is thought to arise from the basal cells of the epidermis, but some scientists speculate that the root sheath cells of the hair follicle are actually the cells of origin because these tumors arise mostly from skin with hair.

SCC is derived from follicle-associated epidermal stem cells, but can behave differently depending on the anatomical location of the skin. Therefore, SCC of the labial border or scar skin behaves more aggressively, metastasizes more rapidly than that of glabrous skin.

Genetic differences in skin cancer

Some families appear to have a history of melanoma, while others have high-risk genetic variants. One of the most commonly tested genes is CDKN2A, but scientists do not recommend using it as a screening test. The reason is that people who test negative, or who don’t test at all, but come from families with multiple cases of melanoma, will also be advised to follow the same screening guidelines.

However, CDKN2A it is a tumor suppressor gene present in 35-40% of familial melanomas. Some scientists have reported that testing for this gene increases the frequency of total skin exams among carriers without the disease, but decreases it among unaffected noncarriers. Those with the disease who were positive for the gene continued to show high levels of adherence to this recommendation.

Genetics, skin cancer and you

Thus, genetic testing for melanoma could induce better carrier screening practices without increasing the incidence of psychological distress or reducing sun protection behaviors.

The risk of melanoma is also higher in the presence of germline variants such as CDK4, MITF extensionAND BAP1. Xeroderma pigmentosum is also linked to increased risks of all three types of skin cancer mentioned here.

Some autosomal dominant genetic variants are associated with a higher risk of skin cancer. Some are part of syndromes, such as Brooke-Spiegler syndrome (BSS), familial cylindromatosis, and familial multiple trichoepithelioma (MFT). These can be linked to the BCC as well as basal cell adenomas.

All three of these diseases have a common factor: the presence of pathogenic variants of CIL gene on 16q12-q13.

Multiple genetic and environmental risk factors participate in the genesis of skin cancer and aging. With just one hour of UV exposure associated with over 100,000-200,000 lesions in cellular DNA, the importance of repair mechanisms is obvious.

The presence of genetic variants that inhibit DNA repair can therefore alter the expression of oncogenes and tumor suppressor genes, helping cancer cells evade cellular regulatory mechanisms and promoting genomic instability. Oncogenes like SMO extension, HRAS extension, kras, ANRAND GLI1along with the included tumor suppressors PTCH1, TP53AND NOTCH1participate in oncogenesis.

References

Further reading

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