| 1. |
- Arver, Brita, et al.
(författare)
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First BRCA1 and BRCA2 gene testing implemented in the health care system of Stockholm
- 2001
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Ingår i: Genetic Testing. - : Mary Ann Liebert Inc. - 1557-7473 .- 1090-6576. ; 5:1, s. 41282-41282
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to optimize the criteria for the BRCA1 and BRCA2 gene testing and to improve oncogenetic counseling in the Stockholm region. Screening for inherited breast cancer genes is laborious and a majority of tested samples turn out to be negative. The frequencies of mutations in the BRCA1 and BRCA2 genes differ across populations. Between 1997 and 2000, 160 families with breast and/or ovarian cancer were counseled and screened for mutations in the two genes. Twenty-five BRCA1 and two BRCA2 disease-causing mutations were found. Various factors associated with the probability of finding a BRCA1 mutation in the families were estimated. Age of onset in different generations and other malignancies were also studied. Families from our region in which both breast and ovarian cancer occur were likely to carry a BRCA1 mutation (34%). In breast-only cancer families, mutations were found only in those with very early onset. All breast-only cancer families with a mutation had at least one case of onset before 36 years of age and a young median age of onset (< 43 years). Other malignancies than breast and ovarian cancers did not segregate in the BRCA1 families and surveillance for other malignancies is not needed, in general. Decreasing age of onset with successive generations was common and must be taken into account when surveillance options are considered.
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| 2. |
- Ericson Lindquist, Kajsa, et al.
(författare)
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Immunohistochemical Loss of the DNA Mismatch Repair Proteins MSH2 and MSH6 in Malignant Fibrous Histiocytomas.
- 2004
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Ingår i: Sarcoma. - 1357-714X. ; 8:4, s. 123-127
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Soft tissue sarcomas (STS) account for less than 1% of all malignancies and constitute a heterogeneous tumor entity in which malignant fibrous histiocytomas (MFH) represent one-third and are characterized by a lack of type-specific differentiation. A defective mismatch repair (MMR) system cause the familial cancer syndrome hereditary non-polyposis colorectal cancer (HNPCC), and since occasional MFH have been described in HNPCC patients we assessed the contribution of defective MMR to the development of MFH.Methods: MMR status was characterized in a series of 209 histopathologically reviewed MFH. Tissue microarray sections from the tumors were immunohistochemically stained for the MMR proteins MLH1, MSH2 and MSH6, and cases with aberrant staining were further characterized for microsatellite instability.Results and Discussion: Two of the 209 STS-a storiform-pleomorphic MFH and a myxofibrosarcoma-showed concomitant loss of MSH2 and MSH6, but retained staining for MLH1 on both cases. The myxoid tumor also had a microsatellite unstable phenotype. These findings, together with previous observations of defective MMR in pleomorphic STS, indicate that these tumors may be part of the HNPCC-associated tumor spectrum and demonstrate that MMR defects occur in a small subset of STS.
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| 3. |
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| 5. |
- Jansson, Mattias, 1973-
(författare)
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Molecular Genetic Studies of Genes Predisposing for Glaucoma
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glaucoma is one of the leading causes of visual impairment in the world. In glaucoma, the patient’s peripheral vision is lost due to progressive and irreversible deterioration of the retinal ganglion cells and atrophy of the optic nerve. The effect on the visual field is gradual and painless, and the progression so slow, that the patient may not notice until a substantial part of the visual field is lost. If left untreated, glaucoma can lead to blindness.In this thesis, genes associated to glaucoma have been analysed in Swedish patients with primary open angle and exfoliative glaucoma. The genes studied were MYOC, oculomedin, GSTM1 and OPTN.The coding sequence of MYOC was analysed and mutations were found in 1% of the primary open angle glaucoma patients. Additionally, a predisposing variant was found in 1% of the patients as well as in 0.5% of the controls. No disease-associated variation was found in the exfoliative glaucoma cases. Mutations were also found in two families affected by glaucoma. The coding sequence of oculomedin was analysed, but none of the variants found were classified as disease causing in either patient group. GSTM1 was analysed for its presence in the patients. No association could be found for either hetero- or homozygous deletions. The coding sequence and haplotype distribution of OPTN was analysed. None of the variants found were classified as disease causing and none of the haplotypes were associated to the disease in either patient group.There are just a few per cent of the Swedish primary open angle glaucoma patients with genetic variation associated to disease, in the genes analysed in this study. No association to exfoliative glaucoma was found. This indicates heterogeneity in the genetics of glaucoma when different subtypes and different populations are compared. Likely, there are genes still to be identified.
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| 6. |
- Nilbert, Mef, et al.
(författare)
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Viktigt att upptäcka ärftliga fall av kolorektal- och endometriecancer. Mutationer hos »HNPCC-individer» kan orsaka flera tumörsjukdomar
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:34, s. 300-3296
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is one of our most common hereditary cancer syndromes and confers an increased risk for several tumor types, with the greatest lifetime risks being for colorectal cancer and endometrial cancer. Hereditary mutations in one of several mismatch-repair (MMR) genes cause the syndrome, and 39 such mutations, involving the genes MLH1, MSH2 and MSH6, have been been characterized in Sweden. Screening programs for HNPCC have been shown to be cost-effective and to prevent cancer. Identification of HNPCC individuals thus allows prevention of additional tumors in the patient as well as in the family.
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| 7. |
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| 8. |
- Salahshor, Sima, et al.
(författare)
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Low frequency of E-cadherin alterations in familial breast cancer
- 2001
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 3:3, s. 199-207
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Tidskriftsartikel (refereegranskat)abstract
- In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heterozygosity (LOH) at the E-cadherin locus, were screened for germline mutations. No pathogenic germline alterations were detected in these individuals. However, a somatic mutation was found (49-2A-->C) in one of the tumours. This tumour showed a pattern of both ductal and lobular histology. Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G-->A; Ala592Thr) was previously found in one family with diffuse gastric cancer, and colon and breast cancer. An allelic association study was performed to determine whether the Ala592Thr alteration predisposes to breast cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic breast cancer patients and 497 control individuals. The frequencies of this alteration were similar in these groups. However, a correlation between the Ala592Thr alteration and ductal comedo-type tumour was seen. These results, together with previously reported studies, indicate that germline mutations and, more commonly, somatic mutations in E-cadherin may have an influence on the behaviour of the tumours, rather than predispose to breast cancer.
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| 9. |
- Zhou, Xiao-Lei, et al.
(författare)
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Definition of candidate low risk APC alleles in a Swedish population.
- 2004
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:4, s. 550-7
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Tidskriftsartikel (refereegranskat)abstract
- Many families experience an apparently inherited increased risk of colorectal cancer (CRC) similar to the known syndromes familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Besides these high-risk syndromes, approximately 10% of all CRC cases come from families with 2 affected 1st-degree relatives, and even 1st-degree relatives to a single case of CRC are at increased risk. Risk subjects from these families frequently show polyps at colonoscopy, which suggests the APC gene as a good candidate susceptibility gene for these attenuated polypotic syndromes. We used the sensitive DHPLC technique to search for possible predisposing germline mutations in the entire APC gene in 91 risk subjects from these high- and low-risk syndromes with unknown predisposing genes. Most exons were also screened for mutations in 96 normal controls and 96 colorectal cancer cases. In our study we probably have identified the most common APC variants in a Swedish population. Among 30 germline variants identified, 1 clearly pathogenic nonsense mutation and 11 putative pathogenic variants (10 missense and one 3' UTR) were found in 20 index patients (22%). Twelve silent as well as 5 intronic variants were considered nonpathogenic. Two of the missense variants found here, E1317Q and D1822V, have previously been related to a difference in risk of colorectal cancer. One variant, 8636C>A, located within the 3' UTR region of the APC gene, was suggested to constitute an additional low risk allele with a similar relative risk as the Jewish I1307K mutation (OR = 1.8; 95% CI, 0.96-3.40). The question of whether all the other variants confer an increased colorectal cancer risk warrants future large association studies.
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