Gastric cancer in individuals with Li-Fraumeni syndrome

Serena Masciari, Akriti Dewanwala, Elena M. Stoffel, Gregory Y. Lauwers, Hui Zheng, Maria Isabel Achatz, Douglas Riegert-Johnson, Lenka Foretova, Edaise M. Silva, Lisa Digianni, Sigitas J. Verselis, Katherine Schneider, Frederick P. Li, Joseph Fraumeni, Judy E. Garber, Sapna Syngal

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Purpose: 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.

Original languageEnglish (US)
Pages (from-to)651-657
Number of pages7
JournalGenetics in Medicine
Issue number7
StatePublished - Jul 2011


  • Li Fraumeni syndrome
  • TP53
  • gastric cancer
  • germline mutations
  • hereditary gastric cancer syndromes

ASJC Scopus subject areas

  • Genetics(clinical)


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