Goldstein A M, Fraser M C, Clark W H, Tucker M A
Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Natl Cancer Inst. 1994 Sep 21;86(18):1385-90. doi: 10.1093/jnci/86.18.1385.
Familial melanoma patients tend to have an earlier age at first melanoma diagnosis, thinner lesions, a different histologic distribution, and a higher frequency of multiple primary melanomas than patients with nonfamilial melanoma. Previous examination of a large melanoma kindred from Texas suggested that although cutaneous malignant melanoma (CMM) was transmitted in an autosomal dominant fashion, there were sex differences in penetrance and disease expression.
This study further evaluated the age at diagnosis, sex difference in penetrance and disease expression, and segregation of familial CMM.
We evaluated the age at diagnosis and transmission of CMM in 23 U.S. white families with CMM/dysplastic nevi who had been followed 5-17 years. We estimated the median and mean ages at diagnosis of invasive melanoma for all individuals, for men and women separately, and by generation. Using the computer program BMDP1L, we also estimated the cumulative probability of an offspring developing CMM as a function of age according to whether the mother or father had melanoma. In addition, we used a life-table approach to estimate the probability that offspring of CMM parents were affected with CMM (penetrance).
The median age at diagnosis in the 23 kindreds (n = 106) was 33 years, substantially less than that of patients with sporadic melanomas in the U.S. white population. For females, the median age at diagnosis was 29 years; for males, it was 36 years. Nine percent of the case patients developed CMM before age 20 compared with 2% in the general population. There was little difference in the transmission pattern of melanoma between males and females in the 23 families, although sons of CMM parents had a higher risk of CMM than daughters of CMM parents. This difference was, however, based on small numbers and was not statistically significant. The penetrance estimates for CMM were high. They rose rapidly from 6% at age 18 to 85% by age 48. The median age at diagnosis of invasive melanoma decreased dramatically in successive generations; the reduction was 11-16 years per generation and was statistically significant (P < .0001).
Although this reduction in median age at diagnosis may result partly from increased surveillance in hereditary melanoma families and the fact that individuals in the younger generations have not yet reached the highest at-risk ages for developing melanoma, the possibility of changes in melanoma risk and risk factors, genetic and/or environmental, across generations should be considered.
与非家族性黑色素瘤患者相比，家族性黑色素瘤患者首次诊断黑色素瘤的年龄往往更小，病损更薄，组织学分布不同，多发原发性黑色素瘤的发生率更高。此前对来自得克萨斯州的一个大型黑色素瘤家族的研究表明，尽管皮肤恶性黑色素瘤（CMM）以常染色体显性方式遗传，但在外显率和疾病表现方面存在性别差异。
本研究进一步评估了诊断年龄、外显率和疾病表现方面的性别差异以及家族性CMM的遗传情况。
我们评估了23个患有CMM/发育异常痣的美国家庭中CMM的诊断年龄和遗传情况，这些家庭已被随访5至17年。我们分别按所有个体、男性和女性以及按代估算了侵袭性黑色素瘤诊断的中位年龄和平均年龄。使用计算机程序BMDP1L，我们还根据母亲或父亲是否患有黑色素瘤，估算了后代患CMM的累积概率随年龄的变化情况。此外，我们采用生命表法估算CMM患者的后代患CMM的概率（外显率）。
23个家族（n = 106）的诊断中位年龄为33岁，显著低于美国白人群体中散发性黑色素瘤患者的诊断年龄。女性的诊断中位年龄为29岁；男性为36岁。9%的病例患者在20岁前患上CMM，而普通人群中这一比例为2%。在这23个家族中，男性和女性黑色素瘤的遗传模式差异不大，尽管CMM患者的儿子患CMM的风险高于CMM患者的女儿。然而，这种差异基于样本量较小，无统计学意义。CMM的外显率估算值较高。从18岁时的6%迅速上升至48岁时的85%。侵袭性黑色素瘤诊断的中位年龄在连续几代中显著下降；每代下降11至16岁，具有统计学意义（P <.0001）。
尽管诊断中位年龄的下降可能部分归因于遗传性黑色素瘤家族中监测的增加以及年轻一代个体尚未达到患黑色素瘤的最高风险年龄，但应考虑跨代黑色素瘤风险及风险因素（遗传和/或环境）发生变化的可能性。
