title: Early-onset of sporadic basal-cell carcinoma: germline mutations in the TP53, PTCH, and XPD genes.
abstract: BACKGROUND
  Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the Western world. The objective of this study was to examine together germline mutations in the TP53, PTCH, and XPD genes as risk factors for developing BCC at a young age. We hypothesized that mutations in these genes significantly increase the risk of early-onset BCC (< or = 35 years).
  
  
  METHODS
  The PCR, DNA sequencing and Restriction Fragment Length Polymorphisms methods were utilized to study eight Puerto Rican patients with a confirmed diagnosis of BCC before age 35.
  
  
  RESULTS
  A novel germline mutation (T:A transversion) was identified at the exon 4, codon 50 of the TP53 gene of one BCC patient. No other mutations were found at the TP53 or PTCH genes. The presence of the XPD mutant allele is associated with a seven-fold increase in risk (OR = 7.0, p = 0.03) for developing BCC prior to age 35. In addition, the DNA Repair Capacity (DRC) of these BCC patients showed a 47% reduction that was significant in relation to age-matched controls (p = 0.021). However, the XPD mutant allele was not associated with the decrease in DRC observed in BCC participants.
  
  
  CONCLUSIONS
  The evaluated population presented BCC before age 35, a phenomenon that is so rare as to make very difficult the study of this subpopulation with a larger sample size. The results of this study, suggest that the XPD Lys751Gln polymorphism may have a significant role in the development of early-onset BCC in the Puerto Rican population.
authors.affiliation: Department of Biology, University of Puerto Rico in Ponce, PR. edubiomed2006@yahoo.com
authors.forename: Edu B
authors.initials: EB
authors.lastname: Suárez-Martínez
authors.forename: Abigail
authors.initials: A
authors.lastname: Ruiz
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Matías
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales
authors.forename: Anayris
authors.initials: A
authors.lastname: Cruz
authors.forename: Deborah
authors.initials: D
authors.lastname: Vázquez
authors.forename: Jaime
authors.initials: J
authors.lastname: Villa
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Matta
mesh_terms: D000328:Adult; D017668:Age of Onset; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013997:Time Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human