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Researchers Identify Genetic Mutations for Hereditary Diffuse Gastric Cancer

A study, published in the June 6 issue of JAMA, has identified novel genetic mutations linked to hereditary diffuse gastric cancer. It states that these mutations are due to both independent mutational events and common ancestry. The study has been released early to coincide with its presentation at the annual meeting of the American Society of Clinical Oncology.

According to background information in the article, gastric cancer is the second most common cause of cancer death worldwide. There are two major variants of this cancer: an intestinal type and a diffuse type. "A decline in the overall incidence of gastric cancer can be attributed primarily to a decrease of the intestinal variant of gastric cancer with the diffuse type remaining stable or possibly even increasing."

Hereditary diffuse gastric cancer (HDGC) is caused by mutations in the gene CDH1, and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer. "The identification of CDH1 mutations offers the opportunity of cancer risk-reduction strategies for unaffected at-risk individuals," the authors write.

Pardeep Kaurah, M.Sc., of the BC Cancer Agency, Vancouver, and colleagues conducted a study to assess the frequency of mutations in the CDH1 gene and whether these mutations occurred due to independent mutational events or common ancestry.

The study included 38 families diagnosed clinically with HDGC, who were analyzed for CDH1 mutations. Twenty-six families had at least two gastric cancer cases with one case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years.

Thirteen mutations (6 novel) were identified in 15 of the 38 families (40 percent detection rate). Two families from this study plus two additiona
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