| 1. |
- Borg, Åke, et al.
(författare)
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Novel germline p16 mutation in familial malignant melanoma in southern Sweden
- 1996
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Ingår i: Cancer Research. - 0008-5472. ; 56:11, s. 500-2497
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Tidskriftsartikel (refereegranskat)abstract
- The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
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| 2. |
- Måsbäck, A, et al.
(författare)
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Clinical and histopathological characteristics in relation to aetiological risk factors in cutaneous melanoma : a population-based study
- 1999
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Ingår i: Melanoma Research. - 0960-8931. ; 9:2, s. 97-189
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Tidskriftsartikel (refereegranskat)abstract
- In this population-based, case-control study from Sweden using data collected from 1988 to 1990, an increased risk of melanoma was associated with the number of sunburns, propensity to freckle, the number of raised naevi and a family history of melanoma. Furthermore, a decreased risk was associated with occupational sun exposure. The purpose of this study was to investigate whether different histopathological features of the melanoma and clinical factors were related to the different aetiological risk factor patterns. All the confirmed primary cutaneous melanomas (n = 366) were included in the study. Both univariate analyses with tests for interaction and multivariate analyses were performed. Patients with melanoma on the trunk and patients with thin melanomas had an excess of close relatives with a history of melanoma (odds ratios [ORs] = 2.7 and 2.3, respectively). A relationship was also seen between melanomas in younger persons and a family history of melanoma (OR = 2.6). The presence of raised naevi on the arm had a tendency to be closer related to melanoma of the nodular type (OR = 4.3) than melanoma of the superficial spreading type (OR = 1.6). Patients with outdoor occupations during summer had a decreased risk of developing melanoma on the extremities. Melanoma diagnosed in patients born before 1939 had an association with sunburns (OR = 1.9) and freckling (OR = 2.0), while melanomas in patients born in 1939 or later were related to a family history of melanoma (OR = 2.2). These results suggest that different histopathological and clinical features of melanoma are associated with different risk factor patterns, which may imply diverging tumour genesis.
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| 3. |
- 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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| 4. |
- Westerdahl, J, et al.
(författare)
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Is the use of sunscreens a risk factor for malignant melanoma?
- 1995
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Ingår i: Melanoma Research. - 0960-8931. ; 5:1, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.
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| 5. |
- Westerdahl, J, et al.
(författare)
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Reproducibility of a self-administered questionnaire for assessment of melanoma risk
- 1996
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Ingår i: International Journal of Epidemiology. - 0300-5771. ; 25:2, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region.METHODS: Repeat questionnaires were completed on two occasions, 1-3 years apart, by 670 randomly selected subjects. In addition, exposure data from a case-control study were used to estimate the effect of misclassification.RESULTS: Overall, there was a fair to good consistency between the answers on the two occasions for the various epidemiological variables. Exposure variables identified as risk factors for melanoma development were reasonably reproducible. The estimated proportion of agreement, A, ranged from 0.74 to 0.92, the average correct classification rate (assuming common sensitivity and specificity), pi, was > or = 0.85 and the kappa coefficient, kappa, ranged between 0.52 and 0.83. However, the question on number of raised naevi on the arm was an exception since it had a lower test-retest reliability (A = 0.62, pi = 0.77, kappa = 0.40). When using data from the case-control study, the effect of the estimated random misclassification was found to only slightly bias odds ratios toward one.CONCLUSION: Our questionnaire, used for assessment for melanoma risk, provided information with fair to good test-retest reliability, and corrected odds ratios were found to be only slightly higher than observed odds ratios.
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| 6. |
- Westerdahl, J, et al.
(författare)
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Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors
- 1996
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Ingår i: British Journal of Cancer. - 0007-0920. ; 73:9, s. 31-1126
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was found that certain specific types of prescribed drugs, i.e. beta-blockers, hydralazines and benzodiazepines, may increase the risk of melanoma development. However, these associations were diminished, at least for benzodiazepines, after controlling for host factors. As these findings are unconfirmed, and may be due to chance or confounding, further studies are warranted. The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits. Our results do not suggest an association between oral contraceptives and melanoma. Furthermore, reproductive factors were not independent risk factors for melanoma. However, increasing number of live births seemed to be protective (P for trend = 0.01). There is a need for further research to be able to draw firm conclusions on the relation between number of live births and melanoma. The results based on histopathological re-examinations and those based on tumour registry data were essentially the same.
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