Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.
Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.
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DOI：
10.1136/jmg.2010.083022
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发表时间：
2011-03
影响因子：
4
通讯作者：
Kraemer KH
中科院分区：
文献类型：
--
作者：
Bradford PT;Goldstein AM;Tamura D;Khan SG;Ueda T;Boyle J;Oh KS;Imoto K;Inui H;Moriwaki S;Emmert S;Pike KM;Raziuddin A;Plona TM;DiGiovanna JJ;Tucker MA;Kraemer KH
在一项为期40年的自然史研究中，我们确定了患有DNA修复缺陷的着色性干皮病（XP）患者的癌症、神经系统变性和死亡率的频率。从1971年到2009年，所有106名在NIH住院的XP患者都从临床记录和随访中进行了评估。在65%（n=69）的皮肤癌患者中，非黑色素瘤皮肤癌（NMSC）增加了10，000倍，黑色素瘤在20岁以下的患者中增加了2，000倍。首次诊断非黑色素瘤皮肤癌（NMSC）时的9岁中位年龄（n=64）显著小于首次诊断黑色素瘤时的22岁中位年龄（n= 38），与一般人群的相对年龄逆转表明NMSC和黑色素瘤之间的不同致癌机制。在最低限度的阳光照射下有明显灼伤的XP患者（n=65）比那些没有发生皮肤癌的患者更不容易发生皮肤癌。这可能与他们从早期接受的极端防晒有关，减少了他们的总紫外线暴露。进行性神经退行性变发生率为24%（n=25），其中XP-D互补组为16/25。最常见的死亡原因是皮肤癌（34%，n=10）、神经变性（31%，n=9）和内部癌症（17%，n=5）。神经退行性病变XP患者死亡时的中位年龄（29岁）显著小于无神经退行性病变XP患者（37岁）（p=0.02）。这项对XP患者进行的39年随访研究表明，DNA修复基因在皮肤癌和神经退行性变的病因学中起着重要作用。
We determined the frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair in a four decade natural history study. All 106 XP patients admitted to the NIH from 1971 to 2009 were evaluated from clinical records and follow-up. In the 65 percent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10,000–fold and melanoma was increased 2,000-fold in patients under age 20. The 9 year median age at diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly younger than the 22 year median age at diagnosis of first melanoma (n= 38), a relative age reversal from the general population suggesting different mechanisms of carcinogenesis between NMSC and melanoma. XP patients with marked burning on minimal sun exposure (n=65) were less likely to develop skin cancer than those who did not. This may be related to the extreme sun protection they receive from an earlier age, decreasing their total UV exposure. Progressive neurologic degeneration was present in 24% (n=25) with 16/25 in complementation group XP-D. The most common causes of death were skin cancer (34%, n=10), neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). The median age at death (29 years) in XP patients with neurodegeneration was significantly younger than those XP patients without neurodegeneration (37 years) (p=0.02). This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the etiology of skin cancer and neurologic degeneration.
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影响因子：
3.9
作者：
Gerstenblith, Meg R.;Goldstein, Alisa M.;Landi, Maria Teresa
通讯作者：
Landi, Maria Teresa
影响因子：
3.6
作者：
Jacyk, WK
通讯作者：
Jacyk, WK
影响因子：
9.8
作者：
Bastiaens, MT;ter Huurne, JAC;Bavinck, NJB
通讯作者：
Bavinck, NJB
影响因子：
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作者：
Gray, DT;Suman, VJ;Roenigk, RK
通讯作者：
Roenigk, RK
影响因子：
3.8
作者：
Goldstein, AM;Landi, MT;Tucker, MA
通讯作者：
Tucker, MA