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V Egilsson

Publications and source records attributed to V Egilsson.

At least 37 records · Page 2Linked to original sources
PubMed1996

High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients.

Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.

Adult↗
PubMed1996

Frequent occurrence of BRCA2 linkage in Icelandic breast cancer families and segregation of a common BRCA2 haplotype.

Cloning of a breast cancer-predisposing gene (BRCA2) on chromosome 13Q12-14 has been reported recently. We analyzed seven large Icelandic breast cancer families with markers from the BRCA2 region. Five families showed strong evidence of linkage. The maximum two-point LOD scores for the five BRCA2-linked families ranged from 1.06 to 3.19. Haplotype analyses revealed a region with identical allele sizes between the families, suggesting that they have inherited the mutation from a common ancestor. Cancer types other than breast cancer occur in individuals, segregating the affected haplotype within these families. This suggests that mutations in the gene may also confer some risk of other malignancies in both males and females.

Aged↗
PubMed1995

Loss of heterozygosity on chromosome 9 in human breast cancer: association with clinical variables and genetic changes at other chromosome regions.

Primary breast tumors were tested for loss of heterozygosity (LOH), on chromosome 9p with microsatellite markers restricted to a 28 cM region including the MTS1 gene. LOH was found with at least 1 marker in 38% of the 201 cases analyzed. A high frequency of deletions was detected at the 9p23-p21 region, indicating a tumor suppressor gene(s) important for breast cancer tumorigenesis. Tumors with and without LOH on 9p were compared with respect to clinico-pathological factors using chi 2 analysis. Tumors with 9p LOH were significantly associated with high S-phase status and aneuploidy, but not with type, node status, estrogen and progesterone receptor content or age of the patients at diagnosis. Survival analysis showed that LOH at 9p did not significantly affect the survival rate of breast cancer patients. Our results indicate that the aberrations on 9p detected in this study are not of independent prognostic value. A significant association was found between LOH at 9p and LOH at chromosomal arms 3p and 6q, which is an additional contribution toward understanding the genetic events in breast tumor pathogenesis.

Alleles↗
PubMed1995

Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13.

In this study we examined loss of heterozygosity (LOH) on chromosome 13q12-13 in 50 tumors from BRCA2 carriers in five families showing strong evidence of linkage to BRCA2. In addition to high frequency of LOH in female breast cancer, LOH was observed in tumors of the prostate, ovary, cervix, colon, male breast, and ureter. All detected losses involved the wild-type chromosome. These results suggest that BRCA2 is a tumor suppressor gene and may be involved in the tumorigenesis of several cancer types in addition to breast cancer.

BRCA2 Protein↗
PubMed1995

High frequency of allelic imbalance at chromosome region 16q22-23 in human breast cancer: correlation with high PgR and low S phase.

The loss of genetic material from a specific chromosome region in tumors suggests that presence of tumor-suppressor genes. Loss of heterozygosity (LOH) or allelic imbalance (AI) on the long arm of chromosome 16 is a known event in sporadic breast cancer. To locate the commonly deleted regions, and therefore (a) candidate tumor-suppressor gene(s), a deletion map of chromosome 16 was made, using 10 microsatellite markers on 150 sporadic breast tumors. The 3 smallest regions of overlap (SRO) were detected on the long arm of chromosome 16. Allelic imbalance was observed with at least one marker in 67% of the tumors. One marker, D16S421, at the 16q22-23 region, showed the highest allelic imbalance, 58%. Tumors with and without AI on 16q were tested for correlation with clinico-pathological features of the tumors such as estrogen- and progesterone-receptor content (ER and PgR), age at diagnosis, tumor size, node status, histological type, S-phase fraction, AI on chromosome 3p, and ploidy. A correlation was found between AI on 16q and high PgR content, also low S-phase fraction (99% confidence limits). A comparison of tumors with and without AI at the D16S421 marker locus revealed a slight correlation with high PgR content. The survival data showed no difference between patients with AI on 16q and those with a normal allele pattern on the long arm of chromosome 16.

Alleles↗
PubMed1995

Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3.

Eight Icelandic breast cancer kindreds were subjected to linkage analyses with respect to 28 microsatellite loci dispersed along the short arm of chromosome 3. Breast tumors derived from these kindreds were concurrently scored for allelic imbalance with ten of the markers. Linkage to most markers could be excluded on the basis of negative LOD scores and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was seen with two of the markers in comparison with results obtained from sporadic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not significantly elevated in the familial tumors. We suggest that the genetic defect responsible for breast cancer susceptibility in these families either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.

Adult↗
PubMed1995

Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations.

We examined DNA from 116 female and four male breast cancer patients for loss of heterozygosity (LOH). DNA was analysed by polymerase chain reaction using ten microsatellite markers on chromosome 11. Three distinct regions of LOH were identified: 11p15.5, 11q13 and 11q22-qter with a LOH frequency of 19, 23 and 37-43% respectively. The marker D11S969 showing the highest frequency of LOH (43%) is located at the 11q24.1-q25 region. No previous molecular genetic studies have shown frequent LOH at the region telomeric to q23 on chromosome 11. Southern analysis revealed that LOH at 11q13 was due to amplification, whereas LOH at 11q22qter was due to deletion. LOH at 11p15.5 was associated with paucity of hormone receptor proteins, high S-phase and positive node status. An association was found between LOH at 11q13 and positive node status. LOH at the 11q22-qter region correlated with a high S-phase fraction. A significant association was found between LOH at 11p15 and chromosome regions 17q21 (the BRCA1 region) and 3p.

Blotting, Southern↗
PubMed1995

Identification of a breast tumor with microsatellite instability in a potential carrier of the hereditary non-polyposis colon cancer trait.

Allelic expansion at microsatellite loci in colorectal tumor DNA indicates a genomic instability caused by defects in DNA mismatch repair. This is observed in a high proportion of tumors from individuals affected by hereditary non-polyposis colorectal carcinoma, but to a lesser extent in sporadic colorectal tumors. In this study we screened 46 colorectal tumors for replication errors (RER). Tumors from six patients were found to be RER positive, two of which had a marked family history of colon cancer. In both cases the RER + phenotype was detected in colon tumors from other family members, suggesting a germline mutation in mismatch repair genes. Additionally, RER + phenotype, distinct from that of the colon and sporadic breast tumors, was found in malignant breast tissue from the mother of one proband.

Adult↗
PubMed1995

Chromosome 17q-linkage seems to be infrequent in Icelandic families at risk of breast cancer.

Eight Icelandic families with multiple cases of breast cancer, and 17 pairs of sisters diagnosed by the age of 50 were analysed for linkage to markers around BRCA1 on chromosome 17q. The sister-pairs are thought to represent a wider population as compared to the larger high-risk families. Tumours were also analysed for LOH involving BRCA1. In accordance with a proposed tumour-suppressive function of BRCA1, and high prevalence of LOH in 'linked' tumours, the paired sisters' tumours were assayed for double LOH events with common alleles retained. No such pair was observed, and LOH events were seemingly randomly distributed at a 38% frequency. This indicates that most or all pairs are due to other genes than BRCA1 or sporadic involvement. Of the eight high-risk families, only one showed convincing evidence of 17q-linkage. Therefore, BRCA1 mutations seem to be a minor explanation of familial risk of breast cancer in Iceland.

Adult↗
PubMed1994

Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q.

Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis. We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus, BRCA1, on chromosome 17q. We found strong evidence against linkage to BRCA1 (lod score-16.63) and the best estimate of the proportion of linked families was 0% (95% CI 0-18%). Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early-onset breast cancer in women and which confers a higher risk of male breast cancer. Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene.

Breast Neoplasms↗
PubMed1993

Linkage analysis of chromosome 17q markers and breast-ovarian cancer in Icelandic families, and possible relationship to prostatic cancer.

Seven families, selected for breast cancer segregation, have been analyzed for chromosome 17q12-q23 linkage to breast and ovarian cancer. In two of them, linkage is seen with most markers tested, increasing toward the most proximal region, but without informative recombinations above NM23. In the remaining families, no linkage is observed. Families with 17q linkage are not easily distinguished by clinical characteristics such as early onset (mean age at diagnosis < or = 45 years) or organs involved. In fact, the family with the highest lod scores (> or = 2.3) belongs to the "later onset" (> 45 years) category of families. Interestingly, prostatic cancer is the most frequent malignancy, after breast cancer, in the families that we studied (13 cases total, all metastasizing) and is especially prevalent in males presumed to carry the trait. Of 16 paternal carriers, 7 (44%) had developed prostatic cancer. Haplotype analysis in families with 17q linkage reveals two further prostatic cases as potential carriers. We propose that breast cancer genes may predispose to prostatic cancer in male carriers.

Adult↗
PubMed1992

Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer.

OBJECTIVE: To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN: Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING: Iceland. SUBJECTS: The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES: Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS: The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS: Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.

Aged↗
PubMed1989

Polymorphism of the c-Ha-ras-1 proto-oncogene in sporadic and familial breast cancer.

Two studies on breast cancer patients are described. Our aim was to examine whether the combined frequency of rare c-Ha-ras-1 alleles in cancer patients was raised. Firstly, the c-Ha-ras-1 locus in 56 breast cancer patients and 48 controls was examined for restriction fragment length polymorphism (RFLP) by Southern blot analysis of leukocyte DNA. Four predominant allelic fragments were found in both groups together with a variety of rare alleles. The 2 groups did not differ significantly in overall distribution of c-Ha-ras-1 alleles. Rare alleles combined were about as frequent in cases (7.1%) as in controls (6.3%). Secondly, 53 members of 3 families having a high incidence of breast cancer were c-Ha-ras-1 genotyped. None of 10 affected members was found to carry a rare c-Ha-ras-1 allele. The only c-Ha-ras-1 allele common to 11 affected members was a 6.8-kb allele which is found in 72% of the controls. Furthermore, this allele was found with equal frequency in affected and non-affected family members.

Adult↗
PubMed1988

Gastric cancer after gastrectomy.

Inhabitants of Iceland who had undergone gastric resection for non-malignant diseases between 1930 and 1974 were identified and followed up at the Icelandic Cancer Registry in order to evaluate the risk of gastric cancer subsequent to gastric resection. There were 1,214 males and 581 females, contributing 30,792 person/years. The results show an overall 1.16-fold, not significant, increase in the relative risk for gastric cancer. In the first 15 years after operation the risk was decreased, 0.49, 95% confidence interval (CI) 0.24-0.90, but from 15 years or more following operation, the risk was 2.17, 95% CI 1.46-3.10. We conclude that for these subjects the risk is not significantly increased. Patients surviving 15 years or more after operation have an increased risk (p less than 0.001), but they do not contribute substantially to the number of gastric cancer patients in Iceland.

Female↗
PubMed1987

Specific polypeptide differences in normal versus malignant human breast tissues by two-dimensional electrophoresis.

Postmitochondrial and cytosolic polypeptides were extracted from human breast tumors and non-malignant breast tissue and analyzed using high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Approximately 800-1000 postmitochondrial and 600-800 silver stained cytosolic polypeptides were detected over the pH range of 4.8 to 7.5 and molecular weight range of 18-120 kDa. The 2D-PAGE patterns of polypeptides from normal and malignant tissue were very similar, although both qualitative and quantitative polypeptide differences were noted. Six cytosolic polypeptides (pI/molecular weight X 10(-3) 5.20/80 kDa, 5.75/43, 6.25/40, 5.43/35, 5.45/34.5, 5.50/34 and 6.15/24 were expressed only in malignant tissues. One constitutive polypeptide, 7.25/52, was not detected in any of the malignant tissue samples. Quantitatively, marked differences in spot density were noted in polypeptides localized mainly in the molecular weight ranges of 22-40 kDa and pI ranges of 5.65-7.00. A general increase in polypeptide expression was noted in malignant tissues as compared to normal. Twenty-two polypeptides were significantly and consistently increased in tumor samples while only one polypeptide was decreased. One polypeptide, p24 (6.15/24) was expressed in greatest concentrations in tumors which also expressed the greatest estrogen receptor content. Expression of p24 was markedly reduced in normal tissue and malignant tissues expressing low levels of estrogen and progesterone receptors.

Biomarkers, Tumor↗
PubMed1986

Catabolite repressive effects of 5-thio-D-glucose on Saccharomyces cerevisiae.

The effect of the glucose analogue 5-thio-D-glucose (5TG) on the yeast Saccharomyces cerevisiae was studied. Derepression of mitochondrial respiratory chain cytochromes, alcohol dehydrogenase (isoenzyme II), NADH dehydrogenase and maltase was inhibited by 0.5-2 mM-5TG. Growth rate was only slightly affected. Ethanol was efficiently produced with 2 mM-5TG in medium initially containing 0.25% glucose. Mutants resistant to the growth inhibitory effects of 5TG on glycerol medium showed resistance to the catabolite repressing effects of glucose. Other mutants, known to be catabolite repression resistant, showed resistance to 5TG. The analogue seems to inhibit derepression of glucose repressible enzymes with greater potency than glucose itself.

Cytochromes↗
PubMed1985

Suppression of temperature sensitive mutations in oncogene-related CDC genes in Saccharomyces cerevisiae by catabolite repression resistance and cytoplasmic petite mutations.

The "start" cell division control genes CDC36 and CDC28 have been reported to contain a certain sequence homology to tissue oncogenes (ets and some protein kinase encoding oncogenes respectively). Here we report that temperature sensitive mutations in these genes are suppressed in cytoplasmic "petite" mutants and catabolite repression resistant mutants.

Genes, Fungal↗