Center for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
J Med Genet. 2011 Apr;48(4):266-72. doi: 10.1136/jmg.2010.086538. Epub 2011 Feb 15.
CDKN2A mutations confer a substantial risk of cutaneous melanoma; however, the magnitude of risk is uncertain.
The study estimated the hazard ratio (HR) and the average age specific cumulative risk (ie, penetrance) of reported melanoma for CDKN2A mutation carriers in case families using a modified segregation analysis of the first and higher degree relatives of 35 population-based cases. The study sample included 223 relatives of 13 melanoma cases diagnosed when aged 18-39 years from Melbourne, Sydney and Brisbane, Australia, and 322 relatives of 22 melanoma cases diagnosed at any age from Yorkshire, UK.
The estimated HR for melanoma for mutation carriers relative to the general population decreased with regions of increasing ambient ultraviolet (UV) irradiance, being higher for the UK than Australia (87, 95% CI 50 to 153 vs 31, 95% CI 20 to 50, p=0.008), and across Australia, 49 (95% CI 24 to 98) for Melbourne, 44 (95% CI 22 to 88) for Sydney, and 9 (95% CI 2 to 33) for Brisbane (p=0.02). Penetrance did not differ by geographic region. It is estimated that 16% (95% CI 10% to 27%) of UK and 20% (95% CI 13% to 30%) of Australian CDKN2A mutation carriers would be diagnosed with melanoma by age 50 years, and 45% (95% CI 29% to 65%) and 52% (95% CI 37% to 69%), respectively, by age 80 years.
Contrary to the strong association between UV radiation exposure and melanoma risk for the general population, CDKN2A mutation carriers appear to have the same cumulative risk of melanoma irrespective of the ambient UV irradiance of the region in which they live.
CDKN2A 突变赋予了个体罹患皮肤黑色素瘤的高风险；然而，其风险程度尚不确定。
本研究通过对来自澳大利亚墨尔本、悉尼和布里斯班的 35 例发病年龄在 18-39 岁的人群中，以及来自英国约克郡的 22 例任何年龄发病的人群中的病例一级和更高亲属进行改良分离分析，估计了 CDKN2A 突变携带者的病例家族中黑色素瘤的风险比（hazard ratio，HR）和平均年龄特异性累积风险（即外显率）。研究样本包括来自澳大利亚墨尔本、悉尼和布里斯班的 13 例 18-39 岁发病的黑色素瘤病例的 223 名亲属，以及来自英国约克郡的 22 例任何年龄发病的黑色素瘤病例的 322 名亲属。
与普通人群相比，突变携带者罹患黑色素瘤的 HR 随环境紫外线（ultraviolet，UV）辐射区域的增加而降低，英国的 HR 高于澳大利亚（87，95%置信区间为 50 至 153 比 31，95%置信区间为 20 至 50，p=0.008），在澳大利亚，墨尔本为 49（95%置信区间为 24 至 98）、悉尼为 44（95%置信区间为 22 至 88）、布里斯班为 9（95%置信区间为 2 至 33）（p=0.02）。地理区域之间的外显率无差异。预计英国的 16%（95%置信区间为 10%至 27%）和澳大利亚的 20%（95%置信区间为 13%至 30%）CDKN2A 突变携带者将在 50 岁前被诊断为黑色素瘤，分别有 45%（95%置信区间为 29%至 65%）和 52%（95%置信区间为 37%至 69%）将在 80 岁前被诊断为黑色素瘤。
与普通人群中紫外线辐射暴露与黑色素瘤风险之间的强关联相反，CDKN2A 突变携带者似乎具有相同的黑色素瘤累积风险，而与他们居住的地区的环境紫外线辐射无关。
