Heerfordt Ida M, Esmann Frederik Viggo Lautrup, Horwitz Henrik
Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark;
Department of Geriatric and Palliative Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Anticancer Res. 2025 Nov;45(11):4683-4687. doi: 10.21873/anticanres.17818.
BACKGROUND/AIM: Actinic keratosis (AK) is a common skin condition associated with cumulative sun exposure and advancing age. As a precursor to squamous cell carcinoma, it is clinically relevant as a target for prevention. While epidemiological studies have suggested various risk factors, causal inference is often limited by confounding. Mendelian randomization (MR), which uses genetic variants as proxies for exposures, can help address this. This review aimed to provide an overview of published MR studies that have examined AK either as an exposure or an outcome.
We conducted a systematic literature search in MEDLINE and Embase from inception to August 2025. Eligible studies were original human research employing MR to investigate associations involving AK and any health-related trait.
Eight studies were included, all of which applied two-sample MR using summary-level genome-wide association data, primarily from European populations. The studies explored a variety of exposures, including metabolic traits, immune cell characteristics, dermatological conditions, and sun sensitivity. One study examined AK as an exposure to assess its association with skin cancers. Most analyses were exploratory, and no exposure-outcome pair was studied in more than one paper, limiting conclusions and precluding meta-analysis.
The body of MR research concerning AK is limited but methodologically diverse. Although the current evidence base is small, this review highlights how MR has been applied to AK and may inform directions for future investigation.
背景/目的：光化性角化病（AK）是一种常见的皮肤疾病，与长期日晒和年龄增长有关。作为鳞状细胞癌的前驱病变，它作为预防目标具有临床相关性。虽然流行病学研究提出了各种风险因素，但因果推断往往受到混杂因素的限制。孟德尔随机化（MR）利用基因变异作为暴露因素的替代指标，有助于解决这一问题。本综述旨在概述已发表的将AK作为暴露因素或结局进行研究的MR研究。
我们对MEDLINE和Embase数据库从建库至2025年8月进行了系统的文献检索。符合条件的研究是采用MR研究AK与任何健康相关特征之间关联的原创性人体研究。
纳入了8项研究，所有研究均使用汇总水平的全基因组关联数据进行两样本MR分析，主要来自欧洲人群。这些研究探讨了多种暴露因素，包括代谢特征、免疫细胞特征、皮肤病状况和日光敏感性。一项研究将AK作为暴露因素来评估其与皮肤癌的关联。大多数分析都是探索性的，没有任何暴露-结局对在一篇以上的论文中进行研究，这限制了结论的得出并排除了荟萃分析。
关于AK的MR研究数量有限，但方法多样。尽管目前的证据基础较小，但本综述强调了MR如何应用于AK，并可能为未来的研究方向提供参考。
