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J Med Genet 48:168-176 doi:10.1136/jmg.2010.083022
  • Original article

Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair

  1. Kenneth H Kraemer2
  1. 1Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, USA
  2. 2Dermatology Branch, National Cancer Institute, Bethesda, Maryland, USA
  3. 3Laboratory of Molecular Technology, National Cancer Institute at Frederick, Science Applications International Corporation, Frederick, Maryland, USA
  4. 4Dermatology Department, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
  1. Correspondence to Dr Kenneth H Kraemer, DNA Repair Section, Dermatology Branch, Center for Cancer Research, National Cancer Institute, Building 37 Room 4002 MSC 4258, Bethesda, MD 20892-4258, USA; kraemerk{at}nih.gov
  • Received 20 July 2010
  • Revised 4 September 2010
  • Accepted 23 September 2010
  • Published Online First 19 November 2010

Abstract

Background The frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a four decade natural history study.

Methods All 106 XP patients admitted to the National Institutes of Health from 1971 to 2009 were evaluated from clinical records and follow-up.

Results In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10 000-fold and melanoma was increased 2000-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 pronounced 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 ultraviolet 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).

Conclusion This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the aetiology of skin cancer and neurologic degeneration.

Footnotes

  • Previous presentations: This study was presented on 8 May 2010 at the American Dermatoepidemiology Network Symposium during the Annual Meeting of the Society of Investigative Dermatology in Atlanta, Georgia, USA. An abstract was published in the Journal of Investigative Dermatology 2010;130:S61.

  • Funding This study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Center for Cancer Research.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the National Cancer Institute, NIH, Bethesda, MD.

  • Provenance and peer review Not commissioned; externally peer reviewed.