患有黑色素瘤的患者中遗传的 MC1R 变体与女性更好的生存相关。
Inherited MC1R variants in patients with melanoma are associated with better survival in women.
机构信息
Dermatology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
出版信息
Br J Dermatol. 2020 Jan;182(1):138-146. doi: 10.1111/bjd.18024. Epub 2019 May 13.
BACKGROUND
Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown.
OBJECTIVES
To evaluate the relationship between germline MC1R status and survival, and determine any association with sex.
METHODS
This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex-related prognosis factors as they relate to features of melanoma and evaluated the sex-specific role of MC1R in overall and melanoma-specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression.
RESULTS
Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38-0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89-1·79; P = 0·185 (P-value for interaction 0·004)]. Analysis performed for melanoma-specific survival showed the same level of significance.
CONCLUSIONS
Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex-dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma-specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow-up and treatment strategies. This provides a basis for understanding the interaction between sex-related genes and germline variants in cancer.
背景
女性的黑色素瘤预后较好，皮肤/头发颜色也更浅。已发现遗传型 MC1R 变体与黑色素瘤预后较好相关，但它与性别的相互作用尚不清楚。
目的
评估种系 MC1R 状态与生存的关系，并确定其与性别的任何关联。
方法
这是一项队列研究，纳入了 1996 年 1 月至 2018 年 4 月期间巴塞罗那 Clinic 医院黑色素瘤科的 1341 例黑色素瘤患者。我们检查了与黑色素瘤特征相关的已知与性别相关的预后因素，并评估了 MC1R 在总体和黑色素瘤特异性生存中的性别特异性作用。使用单变量和多变量 Cox 逻辑回归计算危险比 (HR)。
结果
男性的总体生存率低于女性（P<0·001），而在本队列中，遗传型 MC1R 变体与生存改善无关。然而，在女性中，MC1R 变体的存在与多变量分析中的总体生存率改善相关[HR 0·57，95%置信区间 (CI) 0·38-0·85；P=0·006]，但在男性中无相关性[HR 1·26，95% CI 0·89-1·79；P=0·185（P 值交互作用 0·004）]。黑色素瘤特异性生存的分析显示出相同的显著水平。
结论
遗传型 MC1R 变体与女性黑色素瘤的总体生存率改善相关，但与男性无关。内在的性别依赖性特征可以改变特定基因在黑色素瘤预后中的作用。我们认为，黑色素瘤患者的生存研究应包括按性别和 MC1R 基因型进行分析。
本研究有何新发现？遗传型 MC1R 变体与女性黑色素瘤的总体生存率和黑色素瘤特异性生存率改善相关，但与男性无关。
该研究结果有何意义？这些性别差异可能意味着未来黑色素瘤随访和治疗策略的改变。这为理解性别相关基因与癌症中种系变异体的相互作用提供了基础。
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