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Editorial |

Clinical Implications of Founder and Recurrent CDH1 Mutations in Hereditary Diffuse Gastric Cancer

Kirsten N. Kangelaris, MD; Stephen B. Gruber, MD, PhD, MPH
JAMA. 2007;297(21):2410-2411. doi:10.1001/jama.297.21.2410.
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Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant cancer susceptibility syndrome characterized by early onset diffuse gastric cancer and lobular breast cancer.1 The clinical presentation of this particular form of familial gastric cancer was described more than 40 years ago2 and the phenotype can be dramatic. One descendant of the original Maori kindred from New Zealand died of gastric cancer at the age of 14 years; more than 25 of his relatives have succumbed to cancer.3 In a Michigan family with HDGC, 1 family member died from gastric cancer at the age of 17 years, and numerous other family members died of metastatic disease before reaching age 50 years.4 Fortunately, genetic testing has already transformed the care of families with HDGC, and the tragic outcomes in these 2 representative families can now largely be avoided. Prophylactic gastrectomy has the potential to eliminate the risk of gastric cancer in gene carriers,57 while surveillance and other strategies for breast cancer prevention offer protection to women at risk.8

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