Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria2Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California.
JAMA Dermatol. 2016 Jul 1;152(7):776-82. doi: 10.1001/jamadermatol.2016.0050.
Despite the unquestioned relationship of UV radiation (UVR) exposure and melanoma development, UVR-independent development of melanoma has only recently been described in mice. These findings in mice highlight the importance of the genetic background of the host and could be relevant for preventive measures in humans.
To study the role of the melanocortin-1 receptor (MC1R) and melanoma risk independently from UVR in a clinical setting.
DESIGN, SETTING, AND PARTICIPANTS: Hospital-based case-control study, including genetic testing, questionnaires, and physical data (Molecular Markers of Melanoma Study data set) including 991 melanoma patients (cases) and 800 controls.
Association of MC1R variants and melanoma risk independent from sun exposure variables.
The 1791 participants included 991 with a diagnosis of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5% male). Compared with wild-type carriers, carriers of MC1R variants were at higher melanoma risk after statistically adjusting for previous UVR exposure (represented by prior sunburns and signs of actinic skin damage identified by dermatologists), age, and sex compared with wild-type carriers (≥2 variants, OR, 2.13 [95% CI, 1.66-2.75], P < .001; P for trend <.001). After adjustment for sex, age, sunburns in the past, and signs of actinic skin damage, the associations remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI, 1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI, 1.01-2.21] for r/r, with P values ranging from <.001 to .04 when adjusted for facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47 [95% CI, 1.08-1.99] for R/0 with P values ranging from <.001 to .01 when adjusted for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR, 1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with P values ranging from <.001 to .04 when adjusted for actinic skin damage on the hands).
Carriers of MC1R variants were at increased melanoma risk independent of their sun exposure. Further studies are required to elucidate the causes of melanoma development in these individuals.
尽管紫外线 (UVR) 暴露与黑色素瘤发展之间存在毋庸置疑的关系，但最近在小鼠中描述了 UVR 独立的黑色素瘤发展。这些在小鼠中的发现强调了宿主遗传背景的重要性，并且可能与人类的预防措施有关。
在临床环境中研究黑素皮质素 1 受体 (MC1R) 与黑色素瘤风险之间的关系，而不考虑 UVR。
设计、地点和参与者：基于医院的病例对照研究，包括基因检测、问卷调查和包括 991 名黑色素瘤患者（病例）和 800 名对照在内的身体数据（黑色素瘤分子标志物研究数据集）。
MC1R 变体与独立于阳光暴露变量的黑色素瘤风险之间的关联。
1791 名参与者包括 991 名黑色素瘤诊断患者和 800 名对照患者（平均[标准差]年龄，59.2[15.6]岁；50.5%为男性）。与野生型携带者相比，在统计学上调整了先前的 UVR 暴露（以前的晒伤和皮肤科医生识别的光化性皮肤损伤的迹象表示）、年龄和性别后，携带 MC1R 变体的患者黑色素瘤风险更高与野生型携带者相比（≥2 种变体，OR，2.13[95%CI，1.66-2.75]，P<0.001；P<0.001）。调整性别、年龄、过去的晒伤和光化性皮肤损伤的迹象后，关联仍然显著（OR，1.65[95%CI，1.02-2.67]对于 R/R，OR，2.63[95%CI，1.82-3.81]对于 R/r；OR，1.83[95%CI，1.36-2.48]对于 R/0；OR，1.50[95%CI，1.01-2.21]对于 r/r，P 值范围从<.001 到<.04，当调整面部光化性皮肤损伤时；OR，2.36[95%CI，1.62-3.43]对于 R/r；和 OR，1.47[95%CI，1.08-1.99]对于 R/0，P 值范围从<.001 到<.01，当调整背部光化性皮肤损伤时；和 OR，2.54[95%CI，1.76-3.67]对于 R/r，OR，1.75[95%CI，1.30-2.36]对于 R/0；和 OR，1.50[95%CI，1.02-2.20]对于 r/r，P 值范围从<.001 到<.04，当调整手部光化性皮肤损伤时。
MC1R 变体携带者黑色素瘤风险增加，与他们的阳光暴露无关。需要进一步研究阐明这些个体中黑色素瘤发展的原因。
