Biomedical subjects

K Heinimann

Publications and source records attributed to K Heinimann.

22 records · Page 2Linked to original sources

PubMed1997

Disease expression in Swiss hereditary non-polyposis colorectal cancer (HNPCC) kindreds.

The genetics of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) has recently been established and found to be associated with DNA mismatch repair deficiency. As the molecular basis of this syndrome does not appear to predict any particular disease, we compared families selected according to the "Amsterdam" criteria (AC) against families that were selected because of an aggregation of colonic and extracolonic malignancies (EC), all of which have been observed in HNPCC families. A comparison of the 2 groups revealed that there were significant differences between them. Age at disease onset for both groups was 20-30 years younger than in the general population; however, a normal age distribution was observed for the AC group whereas for the EC group a bimodal distribution was apparent. The prognosis for both groups together did not differ from that of the general population; however, if split, the AC group had a significantly better outcome than the EC group. Furthermore, dividing the AC group into hMSH2- and hMLH1-linked families revealed that there was no difference in severity of disease between these 2 groups with respect to survival and mean age of disease onset. Both the AC and EC groups displayed a similar tumour spectrum with a virtually identical tumour distribution. A significant finding was the over-representation, of brain tumours in this family set, which comprised the third most common malignancy after endometrial and stomach cancer.

Adult↗

PubMed1997

Identification of a modifier gene locus on chromosome 1p35-36 in familial adenomatous polyposis.

Phenotypic variability based on nonallelic heterogeneity is a characteristic feature of the dominantly inherited disease, familial adenomatous polyposis (FAP). A modifying locus, called Mom-1, which strongly influences disease expression has been mapped in the mouse model of FAP to the region of murine chromosome 4, which has synteny to human chromosome 1p35-36. In the present study, this chromosomal region was investigated by using 14 microsatellite markers within a large FAP kindred in which patients harbor the same germ-line mutation but show markedly different disease characteristics. The linkage program MLINK was used to determine whether any correlation exists between these markers and the development of extracolonic symptoms in polyposis coli patients. Depending on the mode of inheritance of the affected locus, a maximum lod score was observed for markers D1S211 and D1S197, reaching 2.08 and 1.77, respectively. The observed values obtained within one large FAP family are supportive of a phenotype-modifying locus within this chromosomal region.

Adenomatous Polyposis Coli↗

PubMed1996

[Lipoprotein(a) and plasma lipids in 429 elderly and very old subjects: significance as risk factor, effect of nutrition and life style].

Lipoprotein(a) [Lp(a)] was discovered in 1962. Lp(a) consists of an LDL particle linked to apolipoprotein(a). The latter shows large genetically determined interindividual variation in size. The close relationship of apo(a) to plasminogen suggests interactions with coagulation. Epidemiological studies established Lp(a) as an independent cardiovascular risk factor. In a follow-up to the Basel Study, we measured Lp(a) in 429 healthy men and women aged 65-95. The influence of nutrition and lifestyle and correlation with plasma lipids and other cardiovascular risk factors was analyzed. The mean concentration was 416 +/- 266 mg/l (median 320 mg/l). Lp(a) concentration did not differ between men and women. In contrast to the simultaneously determined lipid fractions, Lp(a) concentration is lower with increasing age. The correlation with plasma cholesterol is low but statistically significant (p < 0.01). Higher Lp(a) values were associated with a history of myocardial infarction and anticoagulant medication (p < 0.01). Other risk factors did not correlate with Lp(a). There was a low but statistically significant correlation between low Lp(a) and regular intake of vitamin pills. Our results confirm the association of longer life expectancy with low Lp(a) concentration, which are to a large extent independent of external factors. Thus, Lp(a) could be a true longevity gene.

Aged↗

PubMedDate not supplied

Association of extracolonic manifestations of familial adenomatous polyposis with acetylation phenotype in a large FAP kindred.

Familial adenomatous polyposis coli (FAP) has been shown to be associated with germline mutations of the adenomatous polyposis gene (APC) on chromosome 5. Extra-colonic manifestations also occur in FAP and include desmoid tumors, epidermoid cysts and osteomas. The combination of FAP with extracolonic symptoms is commonly referred to as Gardner's syndrome. It remains difficult, however, to predict which patients may have a propensity to develop extracolonic manifestations. The rapid acetylation phenotype is believed to be associated with an increased likelihood of sporadic colorectal cancer, whereas the slow acetylation phenotype is recognized as a predisposing factor for bladder cancer. The slow acetylation phenotype is caused by mutant alleles of the cytosolic enzyme N-acetyltransferase (NAT2). In this study, we determined the NAT2 genotype in members of one large FAP family and three smaller ones all of which had been shown to harbor the same germline APC gene mutation. We observed a significant correlation between slow acetylation genotypes and extracolonic manifestations of the disease. Rapid acetylation genotypes were not overrepresented in colorectal cancer cases in this family as compared to the frequency of this genotype in the normal Caucasian population.

Acetylation↗