Abdominal aortic aneurysm (AAA) is a relatively common disease of the elderly presenting as progressive dilatation of the abdominal aorta. The condition shows a pronounced tendency to cluster in families, indicating a genetic component in the disease aetiology. We have screened the cholesteryl ester transfer protein (CETP) gene, which has been proposed as a candidate gene in AAA, by means of SSCP, DNA sequencing and restriction analysis in a cohort of patients with AAA and a matching control group drawn from the Irish population. The analysis has demonstrated sequence variation at four sites in the CETP gene: an A‐T transversion in exon 9 (producing a Lys309‐Stop codon substitution), a G‐A transition in exon 14 (producing a conservative Va1421‐Ile substitution), a C‐T transition in intron 12 and a G‐A transition in intron 15. None of the last three sites corresponded with sites of functional significance in the protein, suggesting that this reflects neutral polymorphism at the CETP locus. Furthermore, the frequencies of these four polymorphisms in the AAA patient and control groups were not significantly different. These data therefore suggest that CETP may be excluded as a candidate gene in abdominal aortic aneurysm.

A pilot screening programme was undertaken in Ireland aneurysm (AAA) (diameter 3 cm or greater) in the siblings of 120 patients known to have AAA. There were 621 siblings; 270 of them were dead, 32 were over 80 years old and 85 lived outside Ireland, leaving 234 under 80 years of age still living in Ireland who were invited to attend for ultrasonographic screening. Of the 270 siblings who had died, 102 were women and 168 men; eight men (4.8 per cent) had died from ruptured AAA. Only 125 (53.4 per cent) of the 234 siblings agreed to participate in the screening programme, 60 brothers from 31 families and 65 sisters from 35 families. Fifteen (12.0 per cent) of the 125 siblings had an AAA (median size 4.2 (range 3.1-6.8) cm), 13 (22 per cent) of the 60 male siblings and two (3 per cent) of the 65 female siblings. The prevalence of AAA among siblings was not affected by the age or sex of the patient with aneurysm. Seven of the 14 male siblings with hypertension had an AAA, compared with only six of the 46 who were normotensive (P = 0.01). The high incidence of AAA in brothers of affected patients highlights the need to counsel this group on their risk of aneurysm. The relatively low participation rate by siblings in this screening programme indicates that a hospital-based unit is unlikely to be effective in recruiting all patient siblings at risk from an AAA.

Abdominal aortic aneurysm (AAA) is a common disease of the elderly exhibiting a complex aetiology. In a survey of 82 Irish aneurysm patients, compared to 79 age- and sex-matched control subjects, we have investigated a number of potential biochemical and molecular genetic markers which are amenable to analysis from blood specimens and which might have predictive value for AAA. No significant differences were observed between patients and control subjects in relation to serum lipids, leucocyte elastase activity or serum alpha 1-antitrypsin concentration. We have used the polymerase chain reaction to screen the patient and control groups in search of disease-associated genetic variation on chromosome 16, particularly in the region of the Cholesteryl Ester Transfer Protein (CETP) gene. Although variation in allele frequencies was detected between patients and controls at the four marker loci studied, no significant gene-disease associations were detected. The absence of gene-disease associations in our study may indicate that the genetic component in the aetiology of AAA in Ireland differs from that in the UK. Alternatively, it may indicate that the high degree of polymorphism at microsatellite loci may make them unsuitable as markers for the study of gene-disease associations in moderately sized populations. We therefore conclude that the biochemical and molecular genetic markers which we have examined are of no predictive value, and that ultrasonography remains the screening modality of choice for abdominal aortic aneurysm.

C-erB-2 oneoprotein expression detected immunohistochemically in primary breast cancer is a potent poor prognostic variable for patients including Irish women t.2.Also primary C-erB-2 expression indicates hormone resistance in recurrent breast cancer and relative tumour resistance to low intensity chemotherapy with mitoxanthrone (data in press).Forty young women (median age 41 years) had staining for C-erB-2 in their primary tumonrs; 11 showed positive staining and 29 did not.All subsequently had recurrences of breast cancer and were then given intensiv e chemotherapy with doxombicin 40 mg/m 2 intravenously and ifosfamide/ mesna 5 g/m 2 by intravenous infusion over 24 hours, with mesna alone for 8 hours.Cycles repeated at 21 day intervals to a total of 4 cycles in patients with responsive tumours.Response rates in recurrences (82% C-erB-2+VE vs 72% C-erB-2-ve) median response durations, and post-treatment survival were no different between patients on the basis of primary turnout C-erB-2 expression.This strongly suggests that young women with operable breast cancer and expression of C-erB-2 should be selected for intensive doxombicin based nee-adjuvant/adjuvant chemother apy.