Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Invest Dermatol. 2018 Jul;138(7):1620-1626. doi: 10.1016/j.jid.2018.01.021. Epub 2018 Feb 8.
Since 1976, melanoma-prone families have been followed at the National Cancer Institute to identify etiologic factors for melanoma. We compared risks of melanoma and other cancers in 1,226 members of 56 families followed for up to 4 decades with population rates in the Surveillance, Epidemiology, and End Results program. All families were tested for mutations in CDKN2A and CDK4; 29 were mutation-positive and 27 mutation-negative. We compared rates of invasive melanomas, both first and second, by family mutation status, with Surveillance, Epidemiology, and End Results program. Comparing three calendar periods of the study, risk of first primary melanoma decreased slightly. Risks of melanoma after first examination, however, were approximately one-third the risks prior to the first examination in both mutation-positive and mutation-negative families. Among patients with melanoma, risk of a second melanoma was increased 10-fold in all families; risk was somewhat higher in mutation-positive families. Risks of other second cancers were increased only for pancreatic cancer after melanoma in mutation-positive families. Over 4 decades, prospective risk of melanoma has decreased substantially in both mutation-positive and mutation-negative families, when melanoma has greatly increased in the general population.
NCI 02-C-0211, ClinicalTrials.gov ID NCT00040352.
自 1976 年以来,黑色素瘤易感家族一直在国家癌症研究所接受随访,以确定黑色素瘤的病因。我们将 56 个家族的 1226 名成员的风险与监测、流行病学和最终结果计划中的人口率进行了比较,这些家族随访时间长达 40 年。所有家族均接受了 CDKN2A 和 CDK4 突变检测;29 个家族为突变阳性,27 个家族为突变阴性。我们比较了家族突变状态与监测、流行病学和最终结果计划的侵袭性黑色素瘤(包括首次和第二次)的发生率。通过比较研究的三个时期,首次原发性黑色素瘤的风险略有下降。然而,在突变阳性和突变阴性家族中,首次检查后的黑色素瘤风险约为首次检查前风险的三分之一。在患有黑色素瘤的患者中,所有家族的第二次黑色素瘤风险增加了 10 倍;在突变阳性家族中,风险略高。在突变阳性家族中,黑色素瘤后胰腺癌的其他第二癌症风险仅略有增加。在过去的 40 年中,当黑色素瘤在普通人群中大幅增加时,突变阳性和突变阴性家族中黑色素瘤的前瞻性风险都大幅降低。
NCI 02-C-0211,ClinicalTrials.gov ID NCT00040352。