No abstract

Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene encoding the tumour-suppressor E-cadherin (CDH1). We describe the search for CDH1 mutations in 36 new diffuse gastric cancer families. All 16 CDH1 exons, neighbouring intronic sequence and an essential promoter region were screened by DNA sequencing. We detected nine different mutations, seven of which were novel. Of the seven novel mutations, five were identified in families who met the IGCLC clinical criteria for HDGC. Two mutations resulted in a premature stop codon and truncation of the protein. Three mutations affected splice sites; two of the splice-site mutations were shown by RT-PCR to disturb normal CDH1 splicing, while the third splicesite mutation was present in two unrelated HDGC families. The remaining two mutations resulted in amino acid substitutions and impaired the ability of E-cadherin protein to form cellular aggregates and suppress invasion in vitro. Together with the occurrence of extragastric tumours such as lobular breast and colorectal cancer, these findings further extend the types of CDH1 mutations and the spectrum of tumours associated with HDGC.

Familial hypercholesterolaemia (FH) is a common inherited disorder, associated with premature vascular disease. FH may be caused by many different mutations in the low density lipoprotein receptor (LDLR) gene, about 700 mutations have been described, most of which occur rarely and often only in single families. Although particular mutations are prevalent in certain ethnic groups, countries with heterogeneous population bases (such as NZ) may carry a wide variety of mutations; making a gene screening approach the appropriate first step for a mutation detection programme. We have compared SSCP with DHPLC to assess their effectiveness as methods for LDLR mutation detection. Although five novel LDLR mutations were detected by SSCP in patients with FH, DHPLC was more sensitive, with eight novel mutations detected. Six of these mutations (T392M, R419G, Y421N, 1206-1207delCT, 1872delC, and 1943delC) were clustered in exons 9 and 13 of the EGF precursor homology domain, one (679-680delAC) in the ligand binding domain (exon 4) and the eighth (P774H) in the membrane-spanning domain (exon 16). Twenty five mutations were identified in 35 patients in total. Of these, we were able to detect only 64% of mutations by SSCP even though all variants were detected by DHPLC. All patients are heterozygous for the mutations, which is consistent with the clinical phenotypes.

Most placebo-controlled studies testing the hypo-cholesterolaemic action of oat bran have compared high fibre against low fibre diets. To determine whether oat bran had greater cholesterol-lowering action than another source of fibre (wheat bran) we compared the effect of breads of similar total fibre content containing either oat bran or additional wheat bran. Twelve hyperlipidaemic subjects (38-66 years) were stabilised on lipid-lowering diets for at least three months prior to the study. Subjects were given each type of bread for four-week periods in a single-blind, cross-over design. Cholesterol, triglyceride and LDL-cholesterol levels did not change significantly during the oat and wheat bread periods. HDL-cholesterol rose equivalently but only to a just significant level during the oat bran diet. Body weights, lipids and lipoprotein parameters were not significantly different between the two diet periods. Both diet treatments lowered serum cholesterol approximately 4%. We conclude that this oat bran bread consumed as part of a lipid-correcting diet did not influence lipoproteins to any greater extent than wheat bread of similar total fibre content.