title: Gastric cancer in individuals with Li-Fraumeni syndrome.
abstract: OBJECTIVE
  Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline mutations in the TP53 gene. Although sarcomas, brain tumors, leukemias, breast and adrenal cortical carcinomas are typically recognized as Li-Fraumeni syndrome-associated tumors, the occurrence of gastrointestinal neoplasms has not been fully evaluated. In this analysis, we investigated the frequency and characteristics of gastric cancer in Li-Fraumeni syndrome.
  
  
  METHODS
  Pedigrees and medical records of 62 TP53 mutation-positive families were retrospectively reviewed from the Dana-Farber/National Cancer Institute Li-Fraumeni syndrome registry. We identified subjects with gastric cancer documented either by pathology report or death certificate and performed pathology review of the available specimens.
  
  
  RESULTS
  Among 62 TP53 mutation-positive families, there were 429 cancer-affected individuals. Gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported two or more cases of gastric cancer, and six (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies.
  
  
  CONCLUSIONS
  Early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer.
authors.affiliation: Division of Population Sciences, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Masciari
authors.forename: Akriti
authors.initials: A
authors.lastname: Dewanwala
authors.forename: Elena M
authors.initials: EM
authors.lastname: Stoffel
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Achatz
authors.forename: Douglas
authors.initials: D
authors.lastname: Riegert-Johnson
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Edaise M
authors.initials: EM
authors.lastname: Silva
authors.forename: Lisa
authors.initials: L
authors.lastname: Digianni
authors.forename: Sigitas J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: Katherine
authors.initials: K
authors.lastname: Schneider
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Fraumeni
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
mesh_terms: D000328:Adult; D000368:Aged; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53