Dave Lal, MD; Taner Yigit, MD; Jedediah A. Kaufman, MD; Carlos A. Pellegrini, MDSeries Editors: Carlos A. Pellegrini, MD; Brant K. Oelschlager, MD


September 14, 2005


Hereditary gastric cancers are thought to represent 1% of all gastric malignancies. Epidemiology studies have identified a subset of gastric cancer patients who develop a hereditary, diffuse-type gastric cancer at an early age. These cancers have been reported in patients as young as age 14, with a majority presenting before age 40.[1] Hereditary diffuse gastric cancer (HDGC) is defined in members of a family with (1) 2 first- or second-degree relatives with diffuse gastric cancer, one of whom is diagnosed before the age of 50 years; or (2) 3 or more first- or second-degree relatives with diffuse gastric cancer, irrespective of age at onset.[1]

In 1993, Lauren and colleagues[2] published a classification scheme for the stratification of gastric cancers into diffuse and intestinal types. These 2 types of disease differ histologically and epidemiologically. The intestinal type has been declining in developing countries and is more common in elderly patients; environmental insults are thought to be an important factor in development. Conversely, the diffuse type is more common in younger patients and the incidence has remained constant; heredity is thought to play a key role in development.

Mutations in which of the following genes most commonly predispose to HDGC?

  1. RAS gene

  2. RET gene

  3. E-cadherin (CDH-1) gene

  4. C-MYC gene

View the correct answer.


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