Introduction: The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism’s biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence. Objectives: To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort. Materials and Method: A multicenter case–control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer. Results: A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%,p< 0.001), less recreational exposure (sunbathing,p= 0.05, and outdoor sports,p= 0.01), and a lower annual income (p= 0.01), with an increase in tobacco exposure (p< 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use (p< 0.001) and practiced more relaxation activities (p= 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC (p< 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis (p< 0.05). Conclusions: The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.
引言：暴露组概念指代所有有害与有益环境暴露的总和，有助于预测生物体随时间推移产生的生物学反应。日光中的紫外线辐射已被确认为皮肤癌的主要致病因素，而鳞状细胞癌（SCC）是与慢性暴露最常相关的类型之一。然而近年证据表明，生活方式、环境污染及水与食物中的污染物亦可能产生影响。目的：在西班牙人群中研究SCC与日光暴露、环境污染、精神压力及生活方式的关系。材料与方法：开展多中心病例对照研究，由西班牙不同地区的13位皮肤科医生在2020年4月至2022年8月期间招募病例与对照。病例组为经病理确诊的SCC患者，对照组为陪同就诊且无皮肤癌病史的个体。结果：共纳入62例SCC患者与126例对照（男性占比分别为62.9%与33.3%，中位年龄分别为76.46（10.1）岁与55.7（15）岁）。与对照组相比，SCC组有更多户外工作经历（75% vs. 22.4%，p<0.001）、更少娱乐性日光暴露（日光浴p=0.05，户外运动p=0.01）、年收入更低（p=0.01），且烟草暴露水平更高（p<0.001），但在电离辐射或化学暴露等其他致癌物方面无显著差异。对照组每日屏幕使用时间更长（p<0.001）且进行更多放松活动（p=0.03）。膳食因素中仅亚麻酸摄入量增加与咖啡摄入量减少与SCC相关（p<0.05）。部分慢性用药（抗焦虑药、抗抑郁药、β受体阻滞剂、他汀类药物、氢氯噻嗪、ACE抑制剂、二甲双胍及奥美拉唑）亦与SCC存在统计学关联。多变量分析中上述所有变量均保持统计学显著性（p<0.05）。结论：本研究发现在西班牙人群中，除慢性日光暴露外，SCC与多种暴露组相关因素存在显著关联。初级预防策略应针对特定人群，例如对户外工作者需推广防晒行为与减压活动，并对使用特定SCC相关药物的患者加强皮肤光防护。
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