Melanoma, although representing <5% of skin cancers, accounts for more than 80% of deaths from cutaneous malignant neoplasms.1,2 Moreover, the incidence of melanoma continues to increase worldwide.3

Exposure to solar ultraviolet radiation (UVR) is the most recognized environmental risk factor for melanoma development.4,5 Both intermittent and chronic or cumulative sun exposure have been associated with melanoma risk.6 However, UVR does not appear to play a major role in the development of certain melanoma subtypes.7 Environmental risk factors other than UVR exposure remain poorly understood.8

Occupation and place of residence may reflect specific environmental exposures and lifestyle patterns that can interact, overlap, or accumulate over time.

Occupation may influence melanoma risk through occupational UVR exposure.6,9–13 However, several studies suggest that other occupational factors may also contribute to melanoma development.5,8,14,15 In addition, the geographical place of residence may influence melanoma characteristics.16

The aim of this study was to investigate the association between histological subtypes and tumor thickness of cutaneous melanoma with patients’ occupation and place of residence in a cohort of melanoma patients from two referral hospitals in Spain.

A total of 2486 melanoma patients were included in the study. There was a slight predominance of women vs men (50.8% vs 49.2%). The median age was 57 years (IQR, 43–69). Regarding melanoma characteristics, the most frequent histological subtype was SSM (1471 cases [59.2%]), followed by NM (386 [15.5%]), LMM (354 [14.2%]), and ALM (114 [4.6%]). A total of 493 cases (19.8%) were in situ and 1993 (80.2%) were invasive. Among invasive melanomas, the median Breslow thickness was 1.10mm (IQR, 0.60–2.45), with nearly half of the cases ≤1mm (968 [48.6%]). Regarding occupation, the service sector was the most represented (23.1%). Indoor professions predominated (76.9%) vs outdoor professions (23.1%). Regarding place of residence, most patients lived in urban areas (79.2%), followed by suburban (13.3%) and rural areas (7.5%). The median population size of the towns was 36,685 inhabitants (IQR, 13,088–334,887) (Table 1).

In this multicenter study including a large cohort of melanoma patients from two referral hospitals in Spain, we found that, vs SSM, LMM and ALM were significantly associated with workers in the primary sector and in the construction or extraction sector. NM, in contrast, was associated with several heterogeneous occupational groups and with suburban populations. Additionally, thick melanomas were predominantly observed among workers in the construction or extraction sector, whereas they were less common among professions typically associated with higher socioeconomic status. Furthermore, melanomas of intermediate thickness were associated with occupational sectors related to installation, maintenance, repair, and transport.

Several studies have reported that outdoor occupations are associated with an increased risk of melanoma, particularly sun-exposed professions such as farmers and construction workers.6,11–13,19–25 However, other studies from different countries have reported no association—or even an inverse association—between melanoma risk and outdoor occupations.9,10,26,27 These findings highlight the need to explore additional occupational or lifestyle-related risk factors that may contribute to melanoma development.

A large proportion of published studies focus on overall melanoma risk rather than on the distribution of different melanoma subtypes. However, it is well established that melanoma subtypes arise on skin with different UVR-related backgrounds and show distinct molecular and genetic profiles.7,28–31 Tsoutsos et al. examined the relationship between occupational solar exposure (indoor vs outdoor) and the four classic melanoma subtypes.32 Their findings suggested that indoor occupations were associated with an increased risk of nodular melanoma, whereas outdoor occupations showed no clear association with histopathological melanoma subtypes traditionally linked to UVR exposure.32 Given this controversy, several studies have suggested alternative carcinogenic factors involved in melanoma development, including dioxins, aromatic hydrocarbons, pesticides, and ionizing or nonionizing radiation.25,33–36

ALM is well recognized as a melanoma subtype unrelated to sun exposure, as it develops on non–sun-exposed skin and lacks the classical UVR mutational signature.7 Instead, ALM has been associated with other risk factors such as pesticide exposure, pressure, and trauma. Fortes et al. reported that pesticide exposure increased melanoma risk, and that the combination of pesticide exposure and occupational UVR doubled the risk vs pesticide exposure alone.14 In that study, occupational UVR exposure alone was not associated with increased melanoma risk. The authors suggested that UVR exposure may increase skin blood flow and sweating, thereby facilitating pesticide absorption.14

Another potential risk factor for ALM is mechanical pressure or trauma. Several studies have reported that ALM frequently arises in areas of the hands and feet subjected to physical stress.15,37–40 Furthermore, a recent Korean study reported that nearly half of acral melanoma cases occurred in farmers and fishermen.39 These findings suggest that the increased risk of ALM observed in our study among workers in the primary and construction sectors may be related to a combination of factors such as pesticide exposure and repetitive trauma. Although UVR exposure is common in these occupational settings, it is unlikely to play a direct role in ALM pathogenesis.

LMM has traditionally been associated with chronic UVR exposure and typically arises on the head and neck of older individuals.7,41,42 Our findings are consistent with this pattern, as LMM was more frequently observed among workers in the primary sector and in construction or extraction occupations. However, when occupations were stratified simply into indoor versus outdoor categories, a clear association between LMM and occupational chronic UVR exposure could not be confirmed. This finding suggests that additional occupational or environmental factors may also contribute to the development of LMM.

In contrast, NM lacks clearly defined risk factors.7,43 It has been associated with both chronic and intermittent sun exposure, although findings remain inconsistent.7,43,44 In our study, NM showed increased risk across several heterogeneous occupational groups—including service, production, military, primary sector, and construction occupations—suggesting that no single occupational exposure explains this association.

SSM is generally associated with low cumulative sun damage and typically occurs on body areas exposed to intermittent UVR and sunburns.7 Correspondence analysis in our study suggested an association between SSM and occupational clusters characterized by predominantly indoor work and higher socioeconomic status. Although these occupations may not directly increase melanoma risk, they share a common pattern of intermittent sun exposure, likely related to recreational activities. This hypothesis, however, was not specifically evaluated in the present study.

Regarding place of residence, we observed that NM was more frequent among individuals living in suburban areas (2001–10,000 inhabitants). Because the etiologic factors for NM remain poorly understood, definitive conclusions cannot be drawn, and further research is required. To our knowledge, no previous studies have investigated this association.

Correspondence analysis also suggested that ALM and LMM tended to be associated with rural populations, whereas SSM was more frequently associated with urban populations. These findings are consistent with previously reported epidemiologic patterns and risk factors for melanoma subtypes.7,39 However, this association was not confirmed in the multinomial logistic regression analysis.

Socioeconomic status has previously been associated with Breslow thickness, with higher socioeconomic status generally linked to thinner melanomas at diagnosis.45–47 Our findings are consistent with this observation, as occupations associated with thicker melanomas tended to correspond to lower socioeconomic groups.

Previous studies have also reported greater Breslow thickness and more advanced melanoma stages among patients living in rural areas. This has been attributed to factors such as lower physician density, limited access to dermatologic services, longer travel distances to health care facilities, and a higher proportion of biopsies performed by nondermatologists.16,48–51

In our series, although multinomial logistic regression analysis did not identify a statistically significant association between Breslow thickness and place of residence, correspondence analysis suggested a tendency for thinner melanomas in urban populations and thicker melanomas in rural populations. This observation was further supported by the Spearman rank correlation analysis, which showed a weak but statistically significant inverse relationship between population size and Breslow thickness.

This study has several limitations. Because of its retrospective design, potential selection bias and recall bias regarding occupational history cannot be excluded. Additionally, we were unable to control for several potential confounding factors, including nonoccupational UVR exposure such as sunbed use or recreational sun exposure. Skin phototype was also not included in the analysis and may represent an important confounder.

Furthermore, in cases where individuals held multiple occupations during their lifetime, only the predominant occupation was considered. The classification of population size categories may also be somewhat outdated given recent population growth, suggesting that higher thresholds for defining urban populations may be more appropriate.

Nevertheless, stratifying patients by occupation and place of residence provides insight into broader lifestyle and environmental contexts that may contribute to melanoma risk.

In conclusion, this large multicenter study describes the association between histopathological melanoma subtypes and Breslow thickness and patients’ occupation and place of residence. Our findings suggest that occupational and environmental factors may influence melanoma characteristics and highlight the importance of targeted melanoma prevention and screening strategies for high-risk populations. Educational and screening initiatives focusing on specific occupational groups, as well as increased awareness among general practitioners involved in their care, may contribute to earlier melanoma detection and improved patient outcomes.

Melanoma research at Hospital Universitari Arnau de Vilanova de Lleida was funded by grants from ISCIII/FEDER “Una manera de hacer Europa” (PI18/00573 and PI21/00294 to RMM), CIBERONC-CB16/12/00231 to RMM and SG. JAB and CB received predoctoral fellowships from IRBLleida/Diputació de Lleida and Universitat de Lleida, respectively.

The funding sources had no role in the design or conduct of the study; the collection, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

None declared.