title: Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome.
abstract: OBJECTIVE
  Hereditary colorectal cancer is associated most commonly with the hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndromes. We investigated the prevalence of early onset colorectal cancer and the frequency of p53 germline mutations in 64 families from a Li-Fraumeni syndrome (LFS) registry.
  
  
  METHODS
  Patients with documented colorectal cancer and a diagnosis at or before age 50 were included. P53 analyses were performed through germline mutational analyses using standard molecular techniques.
  
  
  RESULTS
  Among the 397 patients and 64 families in the classic LFS registry, a total of 11 patients (2.8%) from 10 different families (15.6%) met criteria for classic LFS and had documented colorectal cancer at less than 50 years of age. The mean age at diagnosis in this group was 33 years and of these patients 4 developed colorectal cancer before age 21 (ages, 9, 11, 15, and 20 y). All families that were tested for p53 mutations (8 of 10) had evidence of germline mutations by sequence analysis; therefore, 12.5% of the total number of families in the registry had colorectal cancer at age less than 50 years and a documented germline p53 mutation. Mutations primarily were missense or nonsense and were located between exons 4-10.
  
  
  CONCLUSIONS
  LFS patients with germline p53 mutations may have an increased susceptibility to colorectal cancer and present up to several decades earlier than the general population. LFS should be considered when a young patient presents with colorectal cancer.
authors.affiliation: Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Wong
authors.forename: Sigitas J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Katherine
authors.initials: K
authors.lastname: Schneider
authors.forename: Lisa
authors.initials: L
authors.lastname: DiGianni
authors.forename: David H
authors.initials: DH
authors.lastname: Stockwell
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Li
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
mesh_terms: D000328:Adult; D017668:Age of Onset; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000150:complications* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors