Multifactorial Analysis of Risk Factors for Skin Cancer

Introduction

Skin cancer is one of the most widespread types of cancer in the current decade. Since the skin is the largest organ of the body, it is understandable why it is the most common cancer type in humans. The skin serves as the first line of defense against external influences and plays a key role in regulating body temperature and protecting internal organs. It is also responsible for the perception of touch, pain and heat, making it one of the most important organs of the human body. In addition, the skin has the ability to regenerate and heal, continuously maintaining its protective function. However, if this ability is impaired, uncontrolled cell proliferation may occur, leading to the development of cutaneous malignancies. Skin cancer often arises as a result of mutations in the DNA of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from sunlight or artificial sources (Leiter et al., 2020).

Skin cancer is generally divided into two main categories: melanoma and non-melanoma skin cancer. Melanoma is an aggressive, less common but highly lethal form of skin cancer. According to American Cancer Society statistics, melanomas make up only 1% of the total number of skin cancer cases, but are responsible for higher mortality. Melanoma develops from melanocytes, cells that produce pigment. The pathological process begins with uncontrolled proliferation of melanocytes, leading to the formation of a malignant tumor. Melanoma can affect any area of the body, but it most commonly occurs in areas exposed to UV radiation, such as hands, face, neck and lips. The prognosis of melanoma is favorable only in cases of early diagnosis; otherwise, metastases occur, leading to high mortality. Among different melanoma subtypes are nodular melanoma, superficial spreading melanoma, acral lentiginous melanoma and lentigo maligna (Dildar et al., 2021).

Non-melanoma skin cancers are the most common and include basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and sebaceous gland carcinoma (SGC). BCC forms in basal cells located in the middle layer of the epidermis, while SCC originates in squamous cells in the upper layers of the epidermis. BCC has a tendency to grow more slowly, while SCC is capable of penetrating deeper skin layers. These malignant cells have a low tendency to metastasize and are less aggressive compared with melanoma. Non-melanoma cancers are usually treated more easily and have a more favorable prognosis (Dildar et al., 2021).

Risk factors for the development of skin cancer

Skin cancer is a multifactorial disease influenced by a complex set of demographic, genetic, environmental and lifestyle factors. Demographic aspects, such as age and sex, play a key role, and the risk of this disease increases with age, especially for non-melanoma types. Men generally have a higher risk of developing skin cancer, which may be related to greater UV exposure due to outdoor work activities. Genetic predispositions, including family history and specific genetic mutations such as CDKN2A mutation, contribute to individual risk of developing skin cancer. Environmental factors, especially UV radiation, inadequate UV protection and frequent use of tanning beds are additional factors contributing to higher melanoma incidence. Lifestyle, including dietary habits, smoking and alcohol consumption, also significantly influences individual skin cancer risk. Occupational exposure to chemicals and other substances, as well as health factors such as a weakened immune system and previous history of skin cancer, are other significant factors to consider when assessing risk factors for the development of skin cancer. Changes in moles or nevi should be monitored, because they may indicate the potential occurrence of cancerous lesions (Wunderlich et al., 2024).

Effective prevention of skin cancer requires a comprehensive approach, which includes primary, secondary and tertiary strategies. Primary prevention focuses on preventing the onset of skin cancer through promotion of healthy behavior, public education and environmental measures, such as use of protective clothing and sunscreens, avoiding tanning beds, and creating shaded public spaces (Perez et al., 2022). Secondary prevention consists of early detection of skin cancer using screening programs, regular dermatological examinations, self-examinations and use of advanced diagnostic tools. Education of healthcare professionals and the public is also crucial. Tertiary prevention focuses on reducing the impact of an already existing disease, through regular clinical follow-up, monitoring recurrences, provision of effective treatment methods and rehabilitation services for patients. Integrated preventive measures can significantly contribute to reducing the incidence and burden of skin cancer, thereby improving public health and patient quality of life (Rojas et al., 2022).

A key factor in skin cancer treatment is early diagnosis. Biopsy is commonly used for skin cancer detection, involving sampling a specimen from a suspicious skin lesion for histopathological examination. However, this procedure is invasive, time-consuming and may be painful for the patient. Modern computer technologies offer comfortable, cheaper and faster alternatives for diagnosing skin cancer symptoms. Various non-invasive techniques, such as digital dermatoscopy, are proposed for examining skin symptoms and distinguishing between melanocytic and non-melanocytic lesions. A common approach to skin cancer detection includes image acquisition, pre-processing, segmentation, feature extraction and subsequent classification (Dildar et al., 2021).

Methodology

The methodology of this paper on risk factors for the development of skin cancer includes a comprehensive analysis of relevant published studies and databases. We identify main factors such as the effect of exposure to sunlight, the effect of genetic predispositions, the role of skin phototype and pigmentation in skin cancer risk, and the impact of occupational exposure on the higher occurrence of melanoma and non-melanoma diseases. The aim is to critically assess the methodological approaches and results of included studies, with emphasis on understanding their contribution to research on the relationship between risk factors and the onset of skin cancer. Based on a meta-analytical approach, we synthesize the findings and discuss their practical implications for prevention and formulation of health policies.

Results

Impact of exposure to sunlight on the risk of developing skin cancer

Ultraviolet light, invisible to the human eye, is a form of electromagnetic radiation present in sunlight’s electromagnetic waves. Its spectrum is conventionally divided into UVA (320 - 400 nm), UVB (280 - 320 nm) and UVC (100 - 280 nm). The UVC spectrum below 280 nm and most UVB between 280 and 310 nm are strongly absorbed by stratospheric ozone. Even so, a small proportion of UVB radiation reaches the surface of the planet, where it can damage DNA in exposed tissues, particularly in the 300 - 320 nm wavelength range. Ultraviolet (UV) radiation causes various types of DNA damage, which can lead to specific mutations and subsequent development of skin cancer in people, often decades after the original exposure. These DNA lesions are the result of UV absorption at different wavelengths. Most of this damage is repaired through nucleotide excision repair, which can be deficient in genetic disorders such as xeroderma pigmentosum (Pfeifer 2020).

Given the high risk of skin cancer associated with UV radiation, studies often examine the relationship between sun exposure and increased melanoma incidence. The study by Seokyung An et al. (2021) systematically analyzed the impact of indoor tanning on increased risk of melanoma and non-melanoma skin cancer (NMSC), with special emphasis on early onset of these diseases in individuals younger than 50 years. Results of this study suggest that use of indoor tanning devices is significantly associated with higher risk for overall skin melanoma and NMSC. Epidemiological studies continually identify a strong correlation between the frequency of tanning salon visits and increased melanoma risk (Seokyunga et al., 2021).

To reduce the risk of melanoma, it is essential to improve awareness of the harmful effects of UV radiation and promote preventive measures. The Slovak study by Dvorštiaková et al. (2020) examined knowledge and attitudes of adults in central Slovakia toward artificial UV radiation, with particular focus on tanning salon visits and protective measures against sun exposure. A high percentage of participants (92.6%) reported using UV protective measures in the form of sunscreen. A significant variability was found in participants’ knowledge of their skin phototype, with 76.0% of study participants able to identify their skin type. This knowledge gap was significant also between genders. The study showed that despite available information and high use of protective measures, there is still insufficient awareness of one’s own skin phototype and its importance for sun protection. Knowledge about risks associated with excessive UV exposure, including tanning bed use, is therefore of fundamental importance for the public.

According to information provided by the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), tanning salons are as harmful to human health as asbestos fibers and tobacco smoke. Therefore, UV radiation has been classified by IARC as carcinogenic to humans. People who attend tanning salons before age 35 have up to a 75% higher risk of developing malignant melanoma. In light of these facts, international medical communities support a ban on tanning bed use for recreational purposes (Dvorštiaková et al., 2020).

Impact of genetic predispositions on the development of skin cancer

Melanoma is an aggressive form of cancer whose occurrence is conditioned by a combination of genetic, epigenetic and environmental factors. In clinical practice, sporadic forms of melanoma predominate, yet hereditary melanomas represent about 10% of cases. (Serman et al., 2022). Hereditary melanoma represents a specific subgroup of melanoma that is associated with genetic predispositions and family history. Approximately 7% to 15% of melanoma cases occur in individuals with a family history, with genetic factors playing a key role. Factors influencing hereditary melanoma risk include shared exposures to sunlight, geographic location, skin phototype and pigmentation, and genetic variants. Some familial melanoma cases are caused by mutations in known high-risk tumor predisposition genes, such as CDKN2A. More than 22% of familial melanoma cases are associated with mutation in the CDKN2A gene, and multiple primary melanomas frequently occur in individuals carrying these mutations. Other syndromes, such as Cowden syndrome with mutations in the PTEN gene, may also predispose to melanoma and other tumors. Genetic variants associated with predisposition to melanoma, such as CDKN2A, TERT, MITF and PTEN, not only increase melanoma risk but are often also somatically mutated in the tumor itself (Toussi et al., 2020).

Impact of occupational exposure on the development of skin cancer

Occupational skin cancer is a serious public health problem. Solar ultraviolet radiation is the main external factor contributing to its development, which has led to the identification of a broad group of outdoor workers as a high-risk population. According to WHO and International Labour Organization (ILO) estimates, occupational UV exposure is common and has a significant impact on deaths and health harms due to NMSC. This occupational risk factor is, according to the global WHO/ILO Comparative Risk Assessment, the third largest professional carcinogen (ILO 2023).

According to Pega et al. (2023), in 2019 about 1.6 billion workers worldwide were exposed to UV radiation, representing 28.4% of the working-age population. In that same year, almost 19,000 people died from NMSC due to outdoor work, with most of these deaths occurring in men. Between 2000 and 2019, the number of NMSC deaths attributable to occupational UV exposure almost doubled—a rise of 88%, from 10,088 deaths to 18,960 deaths. Joint WHO/ILO estimates emphasize the importance of further research and adoption of measures to protect workers from UV radiation, with the aim of reducing health risks associated with this exposure (Pega et al., 2023). In 2022, almost 70,000 people died worldwide from NMSC (IARC 2024).

To prevent skin cancer, often caused by cumulative UV radiation exposure, it is necessary to implement appropriate technical, organizational and staffing measures at the workplace. Evaluating cumulative exposure among outdoor workers requires considering exposure level, type of tasks performed directly in sunlight and adequate preventive measures that workers can adopt. Current research emphasizes the need to improve workers’ sun-protection prevention measures. Dermatology is likely to increasingly focus in the future on the growing number of occupational skin cancer cases. Effective resolution of present and future challenges requires a comprehensive approach, including political support and preventive measures at both community and individual levels, with the aim of achieving lasting transformation in worker health protection (ILO 2023).

Discussion

Skin cancer is a complex disease influenced by many factors, not only by UV exposure itself. While UV radiation plays a significant role in skin cancer development, studies also emphasize the importance of genetic predisposition, lifestyle and use of protective measures. The division of UV radiation into UVA, UVB and UVC indicates different depths of skin penetration and specific DNA damage mechanisms. UVB radiation is more strongly absorbed in epidermal layers and is mainly responsible for burns and most DNA damage, while UVA radiation penetrates deeper into the dermis and is associated with chronic damage and photoaging of the skin. In UV radiation, intensity is important, because higher intensity increases the carcinogenic potential of this radiation. In different parts of the world, there are regions with significantly higher UV intensity compared with other areas. These locations include Australia and some parts of Western and Northern Europe, where sunlight intensity is high, which can increase the risk of developing skin cancer. Strong UV radiation has carcinogenic potential and long-term exposure to this radiation can increase risk for individuals living in these regions. A population epidemiological study by Arnold et al. (2022) states that in 2020 a significant melanoma cancer burden was found concentrated in highly developed countries, where a population of mainly European ancestry with lighter skin pigmentation predominates, which is linked to higher risk and increased sensitivity to the carcinogenic effects of sunlight. In different countries and regions around the world, there were significant geographic differences in incidence and mortality rate, with the highest values recorded in light-skinned populations in Australia/New Zealand, Western and Northern Europe (such as Denmark, Norway and the Netherlands) and North America. Conversely, melanoma was less common in most of Africa, South and Central America and Asia. Epidemiological studies are also important for understanding the spread of skin cancer in different populations and ethnic groups. Comparing disease occurrence and factors affecting its development in different geographical areas can provide valuable information for formulating targeted preventive strategies (Arnold et al., 2022).

On the other hand, there is a trend toward indoor tanning, where people use tanning beds for artificial tanning. The use of tanning beds has become a pronounced trend in many countries, with people turning to artificial tanning regardless of season or amount of natural sunlight. This trend is often motivated by aesthetic reasons, such as the desired tanned appearance without burn risk. Despite tanning beds offering a controlled environment for tanning, their use is associated with increased risk of skin cancer, including aggressive melanoma. Tanning beds emit UV radiation that also has similar carcinogenic effects as sunlight (Dessinioti et al., 2022). In prospective large questionnaire studies, specifically Christensen et al. (2019) in Sweden and Lergenmuller et al. (2019) in Norway, focused on women, a link was identified between tanning bed use and SCC development in women, with this link depending on exposure dose.

Skin cancer may also be related to genetic factors, such as mutations in genes like CDKN2A and others, which can greatly increase predisposition to melanoma and other types of this disease. Genetic factors play a key role in melanoma predisposition. Although genetic changes are not inherited directly from parents to children, there are inherited genetic variants that substantially increase risk of melanoma and other types of cancer. According to the National Cancer Institute, up to 10% of melanoma cases may be caused by these inherited changes. Individuals with these mutations have increased risk of melanoma development during their lifetime, while in some families this risk can be 60 - 90%. Mutations in genes such as CDKN2A, CDK4, TERT, POT1, ACD, TERF2IP, MITF and BAP1 are associated with increased melanoma risk. While some of these mutations are less common, they may predispose to other cancer types. However, researchers are trying to better understand how these genetic factors influence melanoma development and its presentation depending on factors such as age, body localization and others (Fischer 2023).

Another major factor contributing to increased frequency of skin cancer is long-term exposure to solar ultraviolet radiation associated with occupational exposure. Global statistics show a dramatic increase in deaths and morbidity linked to NMSC. The most common forms of NMSC are basal cell carcinoma, squamous cell carcinoma and actinic keratosis (AK). The Italian study by Vimercati et al. (2020) found a higher prevalence of clinical signs of skin aging, such as skin dyschromia and actinic keratoses, in workers with long-term outdoor exposure (26.9%), compared with those working indoors (21.8%) (Vimercati et al., 2020).

In concluding the discussion, it is important to emphasize that combating skin cancer requires a comprehensive approach that includes research, public education, implementation of legislation and support for scientific initiatives focused on prevention and treatment of this serious public health problem. Such an approach allows systematic comparison of different factors and aspects associated with skin cancer without repeating specific study results, but with emphasis on their interpretation and public health significance. Effective implementation of measures to protect from sunlight is essential to reduce the occurrence of skin cancer and protect public health. According to WHO, it is necessary to minimize sun exposure from 10:00 to 16:00, when UV radiation is most intense. These hours are critical for use of sunscreens with a high Sun Protection Factor (SPF; at least 30), which should protect the skin from harmful effects of UV radiation. In addition, use of UV-protective sunglasses is important for protecting the eyes from sun-related eye damage. WHO also recommends limiting visits to tanning beds, since use of artificial UV radiation can significantly increase skin cancer risk.

Implementation of legislative measures to regulate tanning beds and strengthening information campaigns about their harmful effects is therefore necessary. To support skin protection, WHO also recommends protective clothing, which should be available and recommended during hours with high UV index. Such clothing effectively protects the skin from direct sunlight and reduces the risk of sunburn and long-term skin damage. Continuous monitoring and evaluation of the effectiveness of these implemented measures are key to ensuring sustained progress in the fight against skin cancer and protecting public health from harmful sunlight effects. This approach emphasizes the importance of comprehensive preventive strategies and their implementation at a global level (WHO 2017).

Conclusion

Based on our study results, it is evident that skin cancer is a multifactorial disease influenced by a combination of environmental, genetic and occupational factors. Skin cancer is a common and increasing disease mainly caused by UV exposure, with higher risk in outdoor workers and tanning bed users. Genetic predispositions, such as mutations in the CDKN2A gene, increase the risk of hereditary melanoma. The occurrence of melanoma and NMSC has been continuously increasing over recent decades. The World Health Organization (WHO) estimates that by 2025, more than 1.7 million new cases of melanoma and NMSC will be recorded worldwide. Prevention includes minimizing UV exposure, regular dermatological examinations and public education. Early diagnosis and effective treatment are crucial for improving prognosis and reducing disease burden. Coordinated efforts of healthcare professionals and regulatory authorities are necessary for effective control of skin cancer.

Acknowledgment

The work is supported by grants KEGA MŠVVaŠ SR 001UPJŠ-4/2024 and 003UPJŠ-4/2024.

Authors:

MUDr. Dana Kluková Ústav verejného zdravotníctva a hygieny, Lekárska fakulta UPJŠ, Košice MUDr. Dana Kluková Mgr. Simona Miškárová prof. MUDr. Kvetoslava Rimárová, CSc. prof. Mgr. MUDr. Erik Dorko, PhD., MPH, MBA MVDr. Martina Hrubovčák Tejová Ústav verejného zdravotníctva a hygieny, Lekárska fakulta UPJŠ, Košice

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