Abstract：
Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.
摘要：
暴露于紫外线辐射（UVR）会增加皮肤癌的风险。由于UVR暴露会随着时间的推移而积累，较浅的皮肤更容易受到UVR的影响，年龄和肤色是皮肤癌的危险因素。然而,健康皮肤中体细胞突变的测量尚未用于计算皮肤癌风险.在这里，我们开发了一种非侵入性检测方法,该方法可量化暴露于阳光下的健康皮肤中的体细胞突变,并将其应用于1,038名受试者的队列.体细胞突变与其他已知的皮肤癌风险因素相结合，以训练模型来计算风险。最终模型(DNA-皮肤癌风险评估，DNA-SCAR）经过训练可以从年龄预测皮肤癌的个人病史，家族史,肤色和突变计数。突变计数的添加显着改善了模型性能（OR=1.395CI：1.14-1.48；p值=5.3x10-6），并且比肤色做出了更显着的贡献。皮肤癌风险的计算与已知的美国人口患病率相匹配，表明DNA-SCAR校准良好。总之,健康的暴露于阳光下的皮肤中的体细胞突变增加了皮肤癌的风险,突变捕获的风险信息未被其他风险因素考虑.通过粘合剂贴片收集皮肤样品的非侵入性性质支持临床实用性。
