COMMENTARY

Gastric cancer

Genetic aetiology of diffuse gastric cancer: so near, yet so far

K M Sweet¹, H T Lynch²

¹ Clinical Cancer Genetics and Adult Genetics, Division of Human Genetics, The Ohio State University, Columbus, OH, USA
² Department of Preventive Medicine, Creighton University School of Medicine, Omaha, New England, USA

Correspondence to:
Correspondence to:
K M Sweet
Clinical Cancer Genetics and Adult Genetics, Division of Human Genetics, The Ohio State University, 2050 Kenny Road, 8th Floor Tower, Colombus, OH 43221, USA; sweet-3@medctr.osu.edu

Revised version received 15 March 2004

Accepted 15 March 2004

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Commentary on the paper by Brooks-Wilson et al

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Abbreviations: HDGC, hereditary diffuse gastric cancer; IGCLC, International Gastric Cancer Linkage Consortium; HNPCC, hereditary non-polyposis colorectal cancer

Keywords: CDH1 mutation; diffuse gastric cancer; genetic counselling; total gastrectomy

The first 150 words of the full text of this article appear below.

Hereditary diffuse gastric cancer (MIM#137215) is an autosomal dominant disease in which gastric cancer develops at a young age. The first report in the medical literature describing familial clustering of gastric cancer was that of Aldred Warthin in 1913, although this family ("family G") was subsequently shown to have hereditary non-polyposis colorectal cancer (HNPCC).^1–3 Further reports of familial predisposition to gastric cancer were, likewise, indirect and based only on clinical and epidemiological observation. Direct proof of a clear molecular basis for diffuse gastric cancer was identified only 6 years ago, when Parry Guilford and colleagues demonstrated germline inactivating mutation of the CDH1 (E-cadherin) gene in a large New Zealand family of Maori ethnicity with early onset, diffuse gastric cancer.⁴ Shortly thereafter, it was shown that CDH1 inactivating mutation accounted for a proportion of European families with gastric cancer, a few families of Japanese and Korean ethnicity, as well . . . [Full text of this article]

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