Pflugfelder Annette, Yong Xuan Ling Hilary, Jagirdar Kasturee, Eigentler Thomas K, Soyer H Peter, Sturm Richard A, Flatz Lukas, Duffy David L
The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD 4102, Australia.
Center of Dermatooncology, Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany.
Cancers (Basel). 2022 May 13;14(10):2410. doi: 10.3390/cancers14102410.
Melanoma incidence rates are high among individuals with fair skin and multiple naevi. Established prognostic factors are tumour specific, and less is known about prognostic host factors. A total of 556 stage I to stage IV melanoma patients from Germany with phenotypic and disease-specific data were analysed; 64 of these patients died of melanoma after a median follow-up time of 8 years. Germline DNA was assessed by the HumanCoreExome BeadChip and data of 356,384 common polymorphisms distributed over all 23 chromosomes were used for a genome-wide analysis. A suggestive genome-wide significant association of the intronic allele rs7551288A with diminished melanoma-specific survival was detected ( = 2 × 10). The frequency of rs7551288A was 0.43 and was not associated with melanoma risk, hair and eye colour, tanning and total naevus count. Cox regression multivariate analyses revealed a 5.31-fold increased risk of melanoma-specific death for patients with the rs7551288 A/A genotype, independent of tumour thickness, ulceration and stage of disease at diagnoses. The variant rs7551288 belongs to the gene, which encodes Seladin-1, an enzyme involved in the biosynthesis of cholesterol. Further investigations are needed to confirm this genetic variant as a novel prognostic biomarker and to explore whether specific treatment strategies for melanoma patients might be derived from it.
在皮肤白皙且有多个痣的个体中，黑色素瘤发病率较高。已确定的预后因素是肿瘤特异性的，而关于宿主预后因素的了解较少。对来自德国的556例I期至IV期黑色素瘤患者进行了分析，这些患者具有表型和疾病特异性数据；其中64例患者在中位随访8年后死于黑色素瘤。通过HumanCoreExome BeadChip评估种系DNA，并使用分布在所有23条染色体上的356,384个常见多态性数据进行全基因组分析。检测到内含子等位基因rs7551288A与黑色素瘤特异性生存率降低存在全基因组显著关联（= 2 × 10）。rs7551288A的频率为0.43，与黑色素瘤风险、头发和眼睛颜色、晒黑及痣总数无关。Cox回归多变量分析显示，rs7551288 A/A基因型患者黑色素瘤特异性死亡风险增加5.31倍，与肿瘤厚度、溃疡情况及诊断时疾病分期无关。变异体rs7551288属于基因，该基因编码Seladin-1，一种参与胆固醇生物合成的酶。需要进一步研究以确认这种基因变异作为一种新的预后生物标志物，并探索是否可以从中得出针对黑色素瘤患者的特定治疗策略。
