The concept of the exposome refers to all environmental exposures and represents a new approach to studying the role of the environment in human health.1 The incidence of skin cancer has increased over the past 20 years, and an exponential rise of nearly 100% is expected within the next 20 years, leading to epidemic levels of prevalence.2 In Spain, the crude incidence rates of melanoma were 8.8 cases per 100,000 person-years in 2015,3 rising to an estimated 13.1 new cases in 2020.4

Ultraviolet radiation (UVR) has been recognized as the primary etiological agent of skin cancer.5 However, there is growing evidence that environmental pollution and contaminants in water, food, or lifestyle may also play a role. On the other hand, from a holistic health perspective, it is increasingly necessary to consider the influence of stress or sleep on the development of cancer.

The objective of this study was to analyze the association between melanoma and exposome variables related to sun exposure, diet, pollution, stress, and lifestyle in the Spanish population.

A multicenter case–control study conducted by 13 dermatologists from different hospitals in Spain from April 1st, 2020 to August 31st, 2022. The case group consisted of patients diagnosed with melanoma, while the control group included individuals without a past medical history of skin cancer who attended consultations as companions.

Data were collected on age, sex, marital status, income, height, weight, place of residence, occupation, phenotype, phototype, chronic medication, sun exposure, sun protection habits, diet, exposure to pollution, toxic substances, ionizing radiation, stress, hours of exercise, and hours of sleep. Statistical significance was set at p<0.05.

The present exposome analysis in melanoma patients corroborates the role of UVR-related variables, specifically chronic occupational sun exposure and past sun protection habits, especially in individuals with light hair and eye color. Meanwhile, screen time, as a potential marker of indoor activity, acted as a protective factor. Some systemic factors, such as exposure to drugs like acetylsalicylic acid, antidepressants, and ACEIs, as well as certain foods like eggs, and smoking habits, were also associated with melanoma development.

The characteristics of our sample patients are similar to previous reports. Melanoma appears to be more frequent in skin phototypes I and II and is associated with light eye and hair color and freckles.6,7

The melanoma group worked outdoors more than controls. In recent years, interest in occupational UVR exposure has increased, and several studies have reported a higher risk of non-melanoma skin cancer in outdoor workers.8

Exposure, particularly in the workplace, to substances such as pesticides increases the risk of melanoma.9 However, other chemicals and ionizing radiation were not found to be statistically associated occupational risk factors after adjusting for known risk factors, such as nevus count and sun exposure, as observed in our study.10

Although some studies confirm the association between acetylsalicylic acid consumption and melanoma development, as in our sample, others suggest it reduces melanoma risk.11 Antidepressant use was associated with a higher risk of melanoma. Vries et al.12 conducted a comprehensive European study finding that stress, traumatic events, and depression were associated with an increased risk of melanoma. Although ACEIs have been associated with a higher risk of non-melanoma skin cancer due to photoinduced reactions,13 they have not been shown to increase melanoma risk.14

Differences in sun protection measures were observed between groups, with controls using them more frequently. Soto et al.15 compared sun protection behaviors of patients before and after melanoma diagnosis, finding that melanoma patients used fewer sun protection measures before diagnosis, with clothing being one of the least used measures.

Regarding sun protection 15 years prior, most respondents reported using lower SPF sunscreens less frequently, possibly due to poorer awareness of sun damage and its implications. However, controls used higher SPF sunscreens than melanoma patients, supporting the importance of unprotected sun exposure in melanoma development. Additionally, the higher number of sunburns in the melanoma group in the past year supports the relationship between sporadic, intense sun exposure and melanoma.16

Of the 59 dietary components, only egg consumption was associated with melanoma. One study concluded that higher egg consumption confers greater risks of all-cause mortality, cardiovascular disease, and cancer in a non-linear dose–response pattern.17 Conversely, Malagoli et al.18 found an inverse correlation between melanoma risk and the consumption of legumes, olive oil, and eggs.

In the multivariate analysis, screen time, associated with indoor activity, turned out to be a protective factor, supporting the importance of outdoor exposure in melanoma development. Additionally, the melanoma group engaged in more weekly hours of exercise. Many studies have reported higher levels of UVR exposure and, consequently, a higher risk of skin cancer among athletes who practice outdoor sports.19

Finally, regarding smoking habits, although smoking-related skin changes have been described, smoking per se has not been proven to be an independent risk factor for melanoma.20

A limitation of this study is its sample size, and since controls were companions, they may have introduced bias by sharing common exposures with cases. The main strength is the simultaneous evaluation of the association between melanoma and all possible exposome factors.

This analysis confirms that sun exposure, particularly occupational exposure and sunburns, is the exposome variable most strongly associated with melanoma, especially in individuals with light skin and eyes. Insufficient sun protection in the past is a significant risk factor, as is chronic consumption of certain drugs. Specific actions are needed, particularly for outdoor workers, but also for children and individuals engaging in outdoor sports and leisure activities, promoting safe sun behaviors.

Reviewed and approved by the Aragón CEIC; approval C.I. PI19/311.

None declared.

None declared.