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 different varieties of skin cancer, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma.

The incidence of skin cancer is rising steadily worldwide, and mortality from this disease has more than doubled over the decade from 1990 to 2010. Skin cancer is the leading cause of cancer globally, numerically exceeding the sum of all other cancers.

The reasons for this rising trend may include increased UV exposure, other environmental factors, genetic risk factors, better surveillance programs, and earlier diagnosis.

Image Credit: Delovely Pics/Shutterstock.com

Image Credit: Delovely Pics/Shutterstock.com

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

The melanin is packaged into melanosomes, sacs of pigment, which are transferred to the keratinocytes. In POC, they are uniformly scattered throughout the keratinocytes but aggregated within the cells in Whites.

The sun protection factor afforded by skin melanin in Blacks is about 13, vs. 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 POC filters out twice as much UV as the skin in Whites.

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

UV light can still induce photodamage in darker skin, leading to skin cancer. Moreover, a darker skin tone in POC may make it harder to recognize the disease, leading to delayed diagnosis and a worse 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 most deaths related to skin cancer. They are three times more likely to be diagnosed late in the natural history of the disease compared to Whites.

Thus, advanced melanoma is diagnosed in over half of Black patients, and over a quarter of Hispanic patients, compared to just 16% of Whites. Melanoma survival rates at five years are 70% in Black patients vs. 94% for Whites.

This is despite the fact that Black and Hispanic Americans 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 mostly on the palms, soles, 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 receive much solar exposure. In comparison, superficial spreading melanoma is the most frequently occurring type in Hispanics and Whites.

Among POC, Japanese are subject to double the incidence of melanomas, at 2.2 per 100,000, than other Asian races, with the rates being 0.2 and 0.5 in Asian Indians and Chinese, respectively.

Basal cell carcinoma

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

BCC is numerically the leading skin cancer in Whites and ranks second in POC. It comprises almost three of every four skin cancers in Whites but less than one in three among POC. BCC occurs mostly among POC living in sunnier regions, most common among Latinos, Chinese, and Japanese, who are relatively fairer skin than other POC.

Squamous cell carcinoma

SCC is linked to lifetime solar exposure, especially in women. It is a rapidly growing skin cancer, commonly from a pre-existing scar or burns. SCCs are the most common skin cancer in Black Americans and Asian Indians but are in second place 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, secondary to leprosy, non-healing ulcers, and other scarring conditions. In Asians, too, SCC occurs in non-sun-exposed areas. Still, UV light is supposed 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 moles, prior radiation therapy, and albinism all present risk factors for melanoma in POC.

Skin Cancer & Black Skin

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

Again, POC are falsely assumed to be at low risk for skin cancer and are not typically warned to look out for signs of this disease or counseled regarding preventive measures and their crucial importance.

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

Finally, many cases occur in relatively undeveloped regions of the world, where cost and logistical considerations rule out any but basic cancer care. Poor or absent cancer screening facilities allow many cases to be missed.

POC may account for the majority of the US population within a decade or two, emphasizing the need to study skin cancers in minority populations and create awareness of them and evolve guidelines for prevention, diagnosis, and treatment.

The cellular origin of skin cancer

BCC is thought to arise from the basal cells of the epidermis, but some scientists postulate that the root sheath cells of the hair follicle are actually the cells of origin because these tumors arise mainly from hair-bearing skin.

SCC occurs from follicle-associated epidermal stem cells but may behave differently depending on the anatomical location of the skin. Thus, SCC of the lip border or scarred skin behaves more aggressively, metastasizing more rapidly than that from glabrous skin.

Genetic differences in skin cancer

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

However, CDKN2A 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 examinations among carriers without the disease but reduces it among unaffected non-carriers. 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 prompt better screening practices by carriers while not increasing the incidence of psychological distress or reducing sun-protective behaviors.  

Melanoma risk is also higher in the presence of germline variants like CDK4, MITF, and BAP1. Xeroderma pigmentosum is also linked to increased risks of all three types of skin cancer mentioned here.

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

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

Multiple genetic and environmental risk factors participate in the genesis of skin cancers and aging. With a single hour of UV exposure being associated with over 100,000 to 200,000 lesions in the cellular DNA, the importance of repair mechanisms is obvious.

The presence of genetic variants that inhibit DNA repair may thus alter the expression of oncogenes and tumor suppressor genes, helping tumor cells to evade cellular regulation mechanisms and promoting genomic instability. Oncogenes such as SMO, HRAS, KRAS, NRAS, and GLI1, along with tumor suppressors including PTCH1, TP53, and NOTCH1, participate in oncogenesis.

References

Further Reading

 

Last Updated: Jul 1, 2023

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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