Laskar R, Ferreiro-Iglesias A, Bishop D T, Iles M M, Kanetsky P A, Armstrong B K, Law M H, Goldstein A M, Aitken J F, Giles G G, Robbins H A, Cust A E
International Agency for Research on Cancer, Lyon, France.
Leeds Institute of Haematology and Immunology, University of Leeds, Leeds, UK.
Br J Dermatol. 2021 Jun;184(6):1085-1093. doi: 10.1111/bjd.19705. Epub 2021 Feb 18.
Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops.
We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk.
We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls.
When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites.
We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.
黑色素瘤的病因被认为有两条途径，这两条途径由痣和日晒类型决定，并与黑色素瘤发生的解剖部位相关。
我们针对一系列全面的风险因素，包括色素沉着和痣的表型、紫外线辐射暴露和多基因风险，研究了与不同解剖部位黑色素瘤的关联。
我们分析了来自2617例初发侵袭性黑色素瘤患者和975例健康对照者的协调数据，这些数据来自澳大利亚和英国的两项基于人群的病例对照研究。通过使用单一方案进行访谈收集问卷数据，并从DNA样本中得出特定途径的多基因风险评分。我们使用无条件逻辑回归估计调整后的优势比，将每个解剖部位的黑色素瘤病例与所有对照进行比较。
将病例与对照参与者进行比较时，躯干、上肢和下肢的黑色素瘤，有痣与无痣的关联比头颈部更强（P异质性<0·001）。极浅肤色（与橄榄色/棕色皮肤相比）与躯干黑色素瘤的相关性比与其他部位黑色素瘤的相关性弱（P异质性=0·04）。多基因风险在不同解剖部位无显著差异。工作日日晒增加与头颈部黑色素瘤呈正相关，但与其他部位无关。
我们发现了黑色素瘤病因异质性的证据支持双途径假说。这些发现增进了对黑色素瘤风险因素的理解，并可指导预防以及皮肤检查教育和实践。
