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| 2. |
- Hakansson, Sara, et al.
(författare)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 3. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Effects of 1 year of growth hormone therapy on serum lipoprotein levels in growth hormone-deficient adults. Influence of gender and Apo(a) and ApoE phenotypes.
- 1995
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1079-5642. ; 15:12, s. 2142-50
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 5. |
- Oscarsson, J, et al.
(författare)
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Diurnal variation in serum insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations during daily subcutaneous injections of recombinant human growth hormone in GH-deficient adults.
- 1997
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Ingår i: Clinical endocrinology. - 0300-0664. ; 46:1, s. 63-8
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Tidskriftsartikel (refereegranskat)abstract
- Whereas there seems to be little, if any, circadian variation in circulating concentrations of IGF-I and IGFBP-3 in healthy subjects, there are conflicting reports on this issue in GH-deficient patients treated with GH as a daily subcutaneous injection. We have therefore investigated the 24-hour serum profiles of IGF-I and IGFBP-3 concentrations after one week and more than one year of GH treatment.Eleven subjects, with adult onset GH deficiency mainly caused by pituitary adenomas were included in the study.In an open study, six subjects (three women and three men; age (+/-SEM) 41.2 +/- 3.9 years) were investigated after one week of GH therapy and five subjects (three women and two men; age (+/-SEM) 61.4 +/- 3.3 years) were investigated after 13-40 months of GH therapy. The GH injections were given at 2000 h. The subjects were hospitalized for 24-hour blood sampling at 1-hour intervals and serum concentrations of GH, IGF-I and IGFBP-3 were determined.There was a significant diurnal variation in serum IGF-I and IGFBP-3 concentrations both in the subjects who had received GH for one week and in those who had received GH treatment for more than one year. The serum concentrations of IGF-I and IGFBP-3 were highest in the morning and lowest during night-time and early morning. The molar IGF-I/IGFBP-3 ratio varied significantly with time in both groups of patients in a similar way as IGF-I and IGFBP-3 indicating a more pronounced variation in IGF-I compared with IGFBP-3 in response to the GH therapy.Significant diurnal variations in serum IGF-I and IGFBP-3 concentrations occur after one week and more than one year of GH treatment with daily subcutaneous injections. The results indicate that the free fraction of IGF-I may exhibit a diurnal variation.
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| 7. |
- Sun, X F, et al.
(författare)
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A novel p53 germline alteration identified in a late onset breast cancer kindred
- 1996
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Ingår i: Oncogene. - 0950-9232. ; 13:2, s. 11-407
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Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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