Truderung Ole Ah, Sagi Judit C, Semsei Agnes F, Szalai Csaba
Department of Genetics, Cell- and Immunobiology, Semmelweis University H-1089 Budapest, Hungary.
Heim Pal Children's Hospital H-1089 Budapest, Hungary.
Int J Mol Epidemiol Genet. 2021 Oct 15;12(5):71-89. eCollection 2021.
Malignant melanoma is one of the most highly ranked cancers in terms of years of life lost. Hereditary melanoma with its increased familial susceptibility is thought to affect up to 12% of all melanoma patients. In the past, only a few high-penetrance genes associated with familial melanoma, such as and , have been clinically tested. However, findings now indicate that melanoma is a cancer most likely to develop not only due to high-penetrance variants but also due to polygenic inheritance patterns, leaving no clear division between the hereditary and sporadic development of malignant melanoma. Various pathogenic low-penetrance variants were recently discovered through genome-wide association studies, and are now translated into polygenic risk scores. These can show superior sensitivity rates for the prediction of melanoma susceptibility and related mixed cancer syndromes than risk scores based on phenotypic traits of the patients, with odds ratios of up to 5.7 for patients in risk groups. In addition to describing genetic findings, we also review the first results of epigenetic research showing constitutional methylation changes that alter the susceptibility to cutaneous melanoma and its risk factors.
就生命损失年数而言，恶性黑色素瘤是排名最靠前的癌症之一。遗传性黑色素瘤因其家族易感性增加，被认为在所有黑色素瘤患者中占比高达12%。过去，只有少数与家族性黑色素瘤相关的高外显率基因，如 和 ，经过了临床检测。然而，现在的研究结果表明，黑色素瘤很可能不仅是由于高外显率变异，还由于多基因遗传模式而发生，这使得恶性黑色素瘤的遗传性和散发性发展之间没有明确的区分。最近通过全基因组关联研究发现了各种致病性低外显率变异，现在已将其转化为多基因风险评分。与基于患者表型特征的风险评分相比，这些评分在预测黑色素瘤易感性和相关混合癌症综合征方面显示出更高的灵敏度，风险组患者的优势比高达5.7。除了描述基因研究结果外，我们还回顾了表观遗传学研究的首批结果，这些结果表明体质性甲基化变化会改变皮肤黑色素瘤的易感性及其风险因素。
