Skin Cancer Incidence Highest In Patients Experiencing Adversity
Overview
The influence of emotional states on skin conditions is well-recognized, yet the specific impact of stress on the development of skin cancer remains under-explored. This retrospective study aimed to broaden the understanding of skin cancer risk factors by examining the intricate relationship between stressful life events and skin cancer incidence. Methods: The study sample consisted of 268 individuals under dermatological follow-up, divided into three groups: patients in remission from cutaneous melanoma (32%), those diagnosed with non-melanoma skin cancer (30%), and a control group at risk for skin cancer (38%). Participants completed questionnaires about childhood and adulthood life events, and the loss or gain of resources following their most stressful adult event. Multinomial logistic regression was employed to analyze the associations between life events and skin cancer occurrence, along with the mediating and moderating effects of resource loss/gain.
Introduction
Chronic stress, whether from a single life event or recurring incidents, can adversely affect emotional, physiological, and behavioral responses, potentially increasing disease susceptibility and progression. Children, particularly within their first three years, are highly vulnerable to stress and adversity, which can disrupt their physical and mental development across systems like immune, neurological, cardiovascular, and metabolic. Stressful life events (SLEs) have been linked to disease onset, including autoimmune diseases, HIV/AIDS, cardiovascular diseases, and cancer. Research indicates that adverse childhood experiences (ACEs) heighten cancer risk in adulthood, with systematic reviews and meta-analyses showing a correlation between stress-related factors and increased cancer incidence, as well as reduced survival among cancer patients.
Despite the well-documented relationship between stress and various diseases, research on stress and skin cancer remains limited. Skin cancer, including cutaneous malignant melanoma and non-melanoma skin cancers such as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC), has predominantly been attributed to UV exposure and genetic factors. However, there is evidence suggesting a link between psychological distress and skin cancer. Studies have shown associations between skin cancer prevalence and mental health issues, and between major depression and elevated melanoma risk. The immunogenic nature of skin cancer suggests that stress-induced immune dysregulation may increase susceptibility to melanoma. Animal studies support this, with stressed mice showing greater susceptibility to UV-induced SCC. Additionally, the timing of stressors may influence cancer development; for example, BCC patients with a history of severe SLEs and childhood emotional maltreatment exhibited poorer immune responses.
Hobfoll’s Conservation of Resources Theory provides a framework for understanding the impact of resource loss due to SLEs. According to this theory, stress occurs when valued resources are threatened or lost. Individuals with fewer resources are more vulnerable to further loss, highlighting the importance of family, neighborhood, and community support. Those with a history of ACEs may struggle with resource preservation and investment later in life, increasing their vulnerability to stress-related health issues. The theory’s principles have been supported by numerous studies on stress and trauma.
We hypothesize that (1) there is an association between the number of reported life events in childhood and adulthood and the likelihood of developing skin cancer; (2) ACEs are linked to an increased likelihood of experiencing losses from SLEs in adulthood, with (2.1) resource loss from significant adult SLEs partially mediating the association between ACEs and skin cancer occurrence, and (2.2) resource gain moderating the association between resource loss and skin cancer, such that greater resource gain weakens this association.
Methods
Inclusion Criteria:
Participants were recruited from a private dermatology clinic specializing in early skin cancer detection between November 2022 and March 2023. Eligible participants were required to be aged 18 or older and either at risk for or already diagnosed with skin cancer.
Exclusion Criteria:
Individuals were excluded from the study if they had a history of severe autoimmune diseases or encountered language barriers that would impede their participation.
Participants were categorized into three groups:
- Individuals previously diagnosed with melanoma and in remission for at least six months.
- Individuals previously diagnosed with Basal Cell Carcinoma (BCC) and/or Squamous Cell Carcinoma (SCC).
- Individuals at risk of developing skin cancer, characterized by having light skin, hair, and eye color, numerous nevi or freckles, prolonged sun exposure, and a family history of skin cancer (control group).
Also read Reasons Why Screening For Skin Cancer Is Important
Analysis
Group differences were evaluated using SPSS version 26, employing χ² tests and analyses of variance (ANOVA) with Scheffé corrections for multiple comparisons. To explore associations between study variables and skin cancer occurrence, multinomial logistic regressions were conducted using Mplus software version 8.9. These analyses adjusted for age and skin cancer risk factors, and included tests for mediation and moderation hypotheses. Interaction terms were standardized to minimize multicollinearity.
Due to the resource ratings being placed at the end of the questionnaire, 14.6% and 19.8% of participants did not complete the loss and gain of resources sections, respectively. There was insufficient justification for imputing missing values for these variables. Consequently, hypotheses involving these variables were analyzed with a sample size of 215 participants.
Results
The study sample consisted of 268 participants, with 65% female representation. Participants were divided into three groups: 87 (32%) in the melanoma group, 80 (30%) in the BCC/SCC group, and 101 (38%) in the control group. All melanoma patients were diagnosed at an early stage and underwent minimally invasive surgical treatment without metastasis or the need for systemic therapy. The average ages were 66.7 years (±11.8) for the melanoma group, 67.9 years (±9.4) for the BCC/SCC group, and 62.3 years (±12.8) for the control group, with the control group being significantly younger than both cancer groups (F(2,264) = 5.88, p = 0.03).
Demographically, most participants were Israeli-born, married, highly educated, and reported above-average income. Health status ratings were predominantly good or excellent (82%), with 86% engaging in regular exercise and only 7% being current smokers (28% were former smokers). No significant differences were observed among the groups in these health behaviors. However, participants in the melanoma and BCC/SCC groups reported more recent chronic conditions and past non-skin cancer diagnoses.
Significant differences emerged in the number of adverse childhood events (Total-ACEs) and stressful life events in adulthood (SLEs). The melanoma group reported significantly more childhood adverse events compared to both the BCC/SCC and control groups, with a minor, non-significant difference between the BCC/SCC and control groups. After adjusting for age and skin cancer risk factors, only childhood adverse events remained significantly different between the groups (p < 0.001), particularly between the melanoma and control groups (p < 0.001). In contrast, adult life events did not significantly differ among the groups after covariate adjustment, likely due to the correlation between age and adult life events (r = 0.43, p < 0.001).
Regarding resource losses and gains from significant stressful life events in adulthood, the melanoma group reported higher resource losses but not gains. Multinomial regression analysis revealed that each additional childhood stressful life event increased the odds of skin cancer occurrence by 29% for the melanoma group compared to the control group (p = 0.003). For the BCC/SCC group, the increase in odds was weak (3%) and non-significant compared to the control group.
Resource loss was a significant predictor, with every 100-unit increase in resource loss associated with a 63% higher likelihood of melanoma after adjusting for other variables. The interaction between resource loss and gain was not significant, indicating that resource gains did not mitigate the impact of resource loss on skin cancer occurrence. Mediation analysis confirmed that resource loss mediated the relationship between childhood adverse events and skin cancer risk in the melanoma group (Estimate (SE) = 0.07(0.03), 95% CI: 0.01–0.14, p = 0.02), with a weaker, non-significant effect in the BCC/SCC group (Estimate (SE) = 0.04(0.03), 95% CI: -0.01–0.10, p = 0.10).
Conclusion
The interplay between mental and physical health is well-documented, with emotional and mental states significantly influencing physiological well-being, including skin health. Research has identified associations between stressful life events (SLEs) and dermatological conditions such as psoriasis and chronic urticaria, though the causal mechanisms remain unclear. Notably, the potential links between psychological states and skin cancer are underexplored, despite increasing evidence suggesting a connection between stress and skin health. Prevailing skin cancer prevention strategies primarily emphasize sun protection and early detection, alongside genetic risk factors like fair skin.
The current study found a significant association between adverse childhood experiences (ACEs) and the occurrence of skin cancer, even after adjusting for established risk factors. This contrasts with the lack of association observed between adult SLEs and skin cancer. Thus, the first hypothesis, which posited a relationship between the number of reported stressful events and skin cancer incidence, was partially supported. Specifically, the melanoma group, but not the BCC/SCC group, reported a higher number of childhood stressful events compared to the control group.
Understanding the complex mechanisms linking mental and physical health is challenging. Theories such as the allostatic load hypothesis and psychoneuroendocrine immunology, which investigates interactions among the nervous, endocrine, and immune systems, provide insights into these associations. Epigenetics, which studies how environmental factors influence gene expression, reveals that gene mutations alone do not cause cancer; instead, they interact with lifestyle and epigenetic factors. Notably, epigenetic changes, unlike genetic mutations, can potentially be reversed, which is crucial for cancer prevention and treatment.
The study’s second hypothesis, specifically hypothesis 2.1, was supported for the melanoma group. Resource loss from the most significant adult stressful life event partially mediated the relationship between childhood life events and melanoma occurrence. These findings align with existing research highlighting the long-term impact of childhood experiences on psychological, social, and physical health.
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