Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic.

Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally.

Congenital hypertrophy of retinal pigment epithelium in patients with colonic polyps associated with cancer family syndrome.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at-risk individuals.

Dominant genes for colorectal cancer are not rare.

The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0.006 with a lifetime penetrance of 0.

Plasma fibrinogen levels and fibrinogen genotype in non-insulin dependent diabetics.

The association between plasma fibrinogen levels, fibrinogen genotype, and the development of macrovascular disease was studied in 100 patients with non-insulin dependent diabetes mellitus (NIDDM). The mean plasma fibrinogen levels in patients with macrovascular disease was higher than those without, although the difference was not statistically significant (3.67 g l-1, and 3.

Microcephaly, focal segmental glomerulonephritis and marfanoid habitus in two sibs.

Two female sibs aged 15 and 18 years with microcephaly, mental retardation and marfanoid habitus who developed focal segmental glomerulonephritis leading to renal failure are described. This combination of features appears to represent a unique syndrome distinct from previous reports of microcephaly in association with the nephrotic syndrome. The mode of inheritance is likely to be autosomal recessive.

Family history and risk of breast cancer.

The risk of breast cancer in first degree relatives of patients with breast cancer can be derived from family history and is dependent upon the age at diagnosis in the index patient. For the relatives of index patients older than 55, the relative risk is 1.57, if less than 55 the relative risk is 2.

Acrorenal syndrome: further observations.

A 23-year-old female patient with the acrorenal syndrome is described. In addition to acral and renal malformations, she had anomalies of the gastrointestinal and genital tracts. An annular pancreas had caused duodenal obstruction and had been associated with malrotation of the bowel.

Cancer family syndrome associated with multiple malignant melanomas and a malignant fibrous histiocytoma.

A 64-year-old female with the cancer family syndrome suffered from multiple malignant melanomas and a malignant fibrous histiocytoma. She has shown unusually long survival which is a feature of these patients.

Rapid diagnosis of familial defective apolipoprotein B-100 by Amplification Refractory Mutation System.

We report a method for the diagnosis of familial defective apolipoprotein (apo) B-100, using the Amplification Refractory Mutation System (ARMS) and either whole blood or extracted DNA in the polymerase chain reaction. Normal and mutant alleles are identified by using two allele-specific oligonucleotide primers, each with the same common primer, to amplify a 187-bp fragment of the apo B-100 gene. Fragment amplification occurs only when the allele-specific primer matches the nucleotide sequence of the template DNA.

Polymorphisms of the apolipoprotein B and E genes and their possible roles in familial and non-familial combined hyperlipidaemia.

The frequency of polymorphisms of the apolipoprotein (apo) B and E gene loci were studied in 59 patients with primary combined hyperlipidaemia, including 26 with familial combined hyperlipidaemia. Variation at the apo B gene locus was examined using restriction enzymes XbaI, EcoRI, and PvuII. At the apo E gene locus, variation causing the E2, E3, and E4 phenotypes was detected using the polymerase chain reaction in conjunction with allele-specific oligonucleotide probes.

Genetic epidemiology of ovarian cancer: segregation analysis.

The genetic epidemiology of ovarian cancer has been investigated by complex segregation analysis of 462 pedigrees ascertained through a normal consultant. The observed pattern of ovarian cancer is compatible with an autosomal dominant gene. The gene frequency of the abnormal allele is 0.

Genetic evidence that the putative receptor binding domain of apolipoprotein B (residues 3130 to 3630) is not the only region of the protein involved in interaction with the low density lipoprotein receptor.

We have searched for sequence differences in the region of the apolipoprotein B (apo B) gene encoding amino acids 3130-3630 in eight individuals with reduced affinity of low density lipoprotein (LDL) for the normal LDL-receptor. All individuals were hypercholesterolaemic and were selected either on the basis of reduced fractional catabolic rate (FCR) of autologous LDL or substantially reduced binding of their LDL to normal LDL-receptors determined by an in vitro cell growth assay using the U937 macrophage-like cell line. Segments of the apo B gene were amplified by the polymerase chain reaction.

Variation in the apolipoprotein B gene and development of type 2 diabetes mellitus.

Several studies have demonstrated an association between variation in the apolipoprotein (apo) B gene, principally as detected by the XbaI and EcoRI restriction fragment length polymorphisms (RFLPs), and lipoprotein levels or cardiovascular disease. We have examined the frequency of the EcoRI and XbaI RFLPs of the apoB gene in 95 white Type 2 diabetic patients aged between 45 and 80 years in order to ascertain whether variation in this gene may be influencing the development of Type 2 diabetes and associated atherosclerosis through obesity. Neither of the two RFLPs had a significant association with clinically defined cardiovascular disease or with body mass index in our sample.

Disparity between apolipoprotein E phenotypes and genotypes (as determined by polymerase chain reaction and oligonucleotide probes) in patients with non-insulin-dependent diabetes mellitus.

Apolipoprotein (apo) E phenotype and genotype frequencies, due to allelic variation at amino acids 112 and 158, have been investigated in 95 Caucasian non-insulin dependent diabetic patients (NIDDM). Phenotypes were determined by one-dimensional isoelectric focussing (IEF). In this sample, the frequency of the epsilon 2 allele was higher (0.

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom.

To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes.

Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic.

Objective: To introduce and monitor a screening programme for first degree relatives of patients with colorectal cancer based on their calculated lifetime risk.

Design: Lifetime risks were calculated for first degree relatives of patients with colorectal cancer and used to offer screening based on estimated risk.

Setting: A family cancer clinic was set up as part of the North East Thames Regional Genetic Service for relatives of patients who had developed colorectal cancer before the age of 45 and members of families in which multiple cancer had occurred.

Detection of apolipoprotein E polymorphisms using PCR/ASO probes and Southern transfer: application for routine use.

The detection of apolipoprotein E genotypes is of importance both for diagnostic and research purposes. We have previously used the polymerase chain reaction to amplify a specific region of the apolipoprotein E gene which, when used in conjunction with allele specific oligonucleotide probes, permits the detection of the six common apolipoprotein genotypes. In our present report we have modified the above procedure by immobilising the amplified DNA using Southern blotting.

Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia.

Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics.

Circulating levels of low-density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K.

Apolipoprotein (apo) E genotypes by polymerase chain reaction and allele-specific oligonucleotide probes: no detectable linkage disequilibrium between apo E and apo CII.

Allelic sequence variation in the apolipoprotein (apo) E gene has been analysed by means of synthetic oligonucleotide probes that detect single base pair substitutions in the codons for amino acid positions 112 and 158, substitutions that are responsible for the common isoforms. Use of the polymerase chain reaction procedure to amplify a sequence of 330 base pairs of the human apo E gene has permitted the development of a robust method for apo E genotyping. This technique has been used to determine the apo E genotype in 95 individuals in whom the genotype for an apo CII TaqI restriction fragment length polymorphism has also been determined.

Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria.

Serum lipid and lipoprotein concentrations were measured in 18 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose, and glycosylated haemoglobin. Diabetic patients with persistent microalbuminuria were found to have a significantly lower high density lipoprotein (HDL) cholesterol concentration (difference 0.