Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

This is the largest reported series of CDH1 mutation carriers, providing more precise estimates of age-associated risks of gastric and breast cancer that will improve counseling of unaffected carriers. In HDGC families lacking CDH1 mutations, testing of CTNNA1 and other tumor suppressor genes should be considered. Clinically defined HDGC families can harbor mutations in genes (ie, BRCA2) with different clinical ramifications from CDH1. Therefore, we propose that HDGC syndrome may be best defined by mutations in CDH1 and closely related genes, rather than through clinical criteria that capture families with heterogeneous susceptibility profiles.

We have combined data from case control studies designed to test the hypothesis that the c-160a promotor polymorphism in the gene coding for the cell adhesion molecule E-cadherin (CDH1) is associated with stomach cancer. A total of 899 individuals (433 patients and 466 controls) were analyzed. The genotype frequencies did not differ significantly between cases and controls, and the genotype-specific risks were not significantly different from unity, with an odds ratio for heterozygotes compared with the common homozygote of 1.3 (95% CI 0.98 -1.8) and 1.2 (0.68 -2.0) for rare homozygotes compared with common homozygotes. We found no evidence for differences in risk for the intestinal-and diffusetype histopathologic subgroups. © 2002 Wiley-Liss, Inc. Key words: stomach cancer; CDH1; polymorphism; susceptibility E-cadherin plays a critical role in many aspects of cell adhesion, epithelial development and the establishment and maintenance of epithelial polarity. Somatic mutations in the E-cadherin gene (CDH1) have been identified in about 50% of sporadic diffuse gastric tumors and lobular breast cancers, and protein truncating, germline mutations in CDH1 confer a high risk of diffuse gastric cancer, with the gene acting as a classic tumor supressor. [1][2][3][4] Several polymorphisms have been identified in CDH1, 1 of which, c-160a, has been shown to have a functional effect. The a-allele has been shown to decrease the transcriptional efficiency by 68% compared with the c-allele. 5 However, a more recent study reported no association between the a-allele risk of breast cancer and found that that the effect of the a-allele on transcription was small. 6 Nevertheless, this polymorphism is a good candidate for susceptibility to stomach cancer, and we have combined the data from 3 separate, small case-control studies to test this hypothesis. MATERIAL AND METHODS Cases and controlsCanadian study. Gastric cancer cases were identified through a search of the pathology archives of the Vancouver Hospital. Cases were selected for analysis if they had either lymph nodes or mucosal margins that were negative for malignancy (n ϭ 148). The mean age of the cases was 65 years (range 23-86 years). DNA was extracted from histologically normal paraffin-embedded tissue using a Qiagen kit (Hilden, Germany). Germline DNA from 93 anonymous normal controls was obtained from a pediatric molecular diagnostics laboratory.The E-cadherin gene promoter polymorphism c-160a was detected by restriction fragment length polymorphism (RFLP) analysis of a 189 bp DNA fragment amplified from the E-cadherin gene proximal promoter region. The PCR amplicon was obtained using the previously published primers 5Ј-TCCCAGGTCTTAGT-GAGCCA-3Ј and 5Ј-GGCCACAGCCAATCAGCA-3Ј and cycling conditions. 5 The PCR products were digested with BstE2 and Af III. BstE2 specifically cleaves fragments with the c-allele, and Af lII specifically cleaves fragments with the a-allele. The fragments were discriminated on a 3% agarose gel.German study. Eligible cases (n ϭ 133) were tho...

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The cotton defoliant, thidiazuron, 1‐phenyl‐3‐(1,2,3‐thiadiazol‐5‐yl)‐urea stimulated ethylene formation in primary leaves of Phaseolus vulgaris var. Favorit, three to eight days after spraying. Aminoethoxyvinylglycine (AVG), an inhibitor of ethylene formation, delayed this ethylene outburst by two to three days when sprayed together with the defoliant. Under conditions of dryness, thidiazuron inhibited the stomatal closure of bean leaves. Spraying with AVG counteracted this effect of thidiazuron on the stomates and caused a partial and reversible closure ca 1 day after spraying.