| 1. |
- Karunaratne, P M, et al.
(författare)
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Analysis of Swedish male breast cancer family data : a simple way to incorporate a common sibling effect
- 1998
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Ingår i: Genetic Epidemiology. - 0741-0395. ; 15:2, s. 12-201
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Tidskriftsartikel (refereegranskat)abstract
- Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.
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| 2. |
- Måsbäck, A, et al.
(författare)
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Cutaneous malignant melanoma in southern Sweden 1965, 1975, and 1985. Prognostic factors and histologic correlations
- 1997
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Ingår i: Cancer. - 0008-543X. ; 79:2, s. 275-283
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a worldwide increase in the incidence of cutaneous malignant melanoma (CMM) among whites. In Sweden, a five-fold increase has been recorded since 1960, although the increase in mortality rate is substantially lower. Tumor thickness is recognized as the most important histologic prognostic factor for primary melanoma. In a previous study, the authors did not find any significant decrease in mean tumor thickness over the period 1965-1985 in their region. In the current study, prognostic factors for melanoma were evaluated for this time period.METHODS: In a population-based study, 468 cases of invasive melanoma, diagnosed in the years 1965, 1975, and 1985, were histopathologically reexamined. The level of invasion, tumor thickness, regressive reaction, ulceration, presence of inflammatory cells, presence of benign nevus cells, and site of presentation were studied. In 461 of these 468 patients, it was possible to correlate the histopathologic factors with survival.RESULTS: In univariate analyses, the parameters of presence of ulceration, increasing tumor thickness, male gender, nodular type of melanoma, and older age at diagnosis were significantly related to a shortened overall survival. In various multivariate models with adjustment for age and the factors studied simultaneously, ulceration, increasing tumor thickness, and male gender were significantly associated with a poor prognosis. Correlations between the factors studied were noted. It was observed that older patients tended to have thicker tumors. Thick melanomas correlated to a deeper level of invasion (Clark's), nodular growth pattern, ulceration, less inflammation, and less regression compared with thin, less invasive melanomas. Women had significantly fewer inflammatory cells and fewer signs of regression in their tumors compared with men.CONCLUSIONS: In multivariate analyses adjusted for age, increasing tumor thickness, older age, ulceration, and male gender were significantly associated with a poor prognosis among patients with invasive CMM. None of these factors showed a significant change for the years 1965, 1975, and 1985. Thus, a change in the prognostic factors studied does not explain the increased survival of melanoma patients for this time period.
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| 3. |
- Olsson, H, et al.
(författare)
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Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors
- 1996
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 40:2, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.
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| 4. |
- Planck, M, et al.
(författare)
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hMLH1, hMSH2 and hMSH6 mutations in hereditary non-polyposis colorectal cancer families from southern Sweden
- 1999
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Ingår i: International Journal of Cancer. - 0020-7136. ; 83:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- We have screened 17 Southern Sweden individuals/families with suspected hereditary non-polyposis colorectal cancer (HNPCC) for mutations in the DNA-mismatch repair genes hMLH1, hMSH2 and hMSH6 using denaturing gradient gel electrophoresis, protein truncation test and direct DNA sequencing. The families were selected on the basis of a family history of HNPCC-related tumors or the occurrence of metachronous colorectal cancer/endometrial cancer at young age in an individual with a weak family history of cancer. Furthermore, we required that tumor tissue from at least one individual in the family had to display microsatellite instability. We identified germ-line mutations in 9 individuals from 8 families. Five families had mutations in hMLH1, 4 of which were splice site mutations, 2 had frameshift mutations in hMSH2 and 1 patient with metachronous endometrial and rectal cancer but with a weak family history of cancer had a nonsense mutation in hMSH6. Our results present novel germ-line DNA-repair gene mutations, one of these in hMSH6, and demonstrate the diversified mutation spectrum in Sweden, where no founder mutation has so far been identified.
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| 5. |
- Rudolph, P, et al.
(författare)
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Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer
- 1999
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 91:3, s. 8-271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis.METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size.RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold.CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.
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| 6. |
- 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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