title: Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland 20892-4258, USA.
authors.forename: Porcia T
authors.initials: PT
authors.lastname: Bradford
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Deborah
authors.initials: D
authors.lastname: Tamura
authors.forename: Sikandar G
authors.initials: SG
authors.lastname: Khan
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boyle
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Oh
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inui
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Moriwaki
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Pike
authors.forename: Arati
authors.initials: A
authors.lastname: Raziuddin
authors.forename: Teri M
authors.initials: TM
authors.lastname: Plona
authors.forename: John J
authors.initials: JJ
authors.lastname: DiGiovanna
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics* / Q000401:mortality; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics* / Q000401:mortality; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D044102:Receptor, Melanocortin, Type 1