| 1. |
- Lindqvist, P. G., et al.
(author)
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Avoidance of sun exposure as a risk factor for major causes of death : A competing risk analysis of the Melanoma in Southern Sweden cohort
- 2016
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 375-387
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Journal article (peer-reviewed)abstract
- Objective: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. Methods: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. Results: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. Conclusion: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.
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| 2. |
- Borg, Åke, et al.
(author)
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High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families
- 2000
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In: Journal of the National Cancer Institute. - 0027-8874. ; 92:15, s. 6-1260
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Journal article (peer-reviewed)abstract
- BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to the occurrence of other cancer types.METHODS: : The entire CDKN2A coding region and exon 2 of the CDK4 gene of an affected member of each of 52 families from southern Sweden with at least two cases of melanoma in first- or second-degree relatives were screened for mutations by use of polymerase chain reaction-single-strand conformation polymorphism analysis. Statistical tests were two-sided.RESULTS: : CDKN2A mutations were found in 10 (19%) of the 52 families. Nine families carried an identical alteration consisting of the insertion of arginine at position 113 of p16(INK4a), and one carried a missense mutation, in which the valine at position 115 was replaced with a glycine. The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. Six of the 113insArg families had at least one member with multiple primary melanomas; the 113insArg families also had a high frequency of other malignancies-in particular, breast cancer (a total of eight cases compared with the expected 2.1; P =.0014) and pancreatic cancer (a total of six cases compared with the expected 0.16; P<.0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations.CONCLUSIONS: : Our findings confirm that the majority of CDKN2A-associated melanoma families in Sweden are due to a single founder mutation. They also show that families with the CDKN2A 113insArg mutation have an increased risk not only of multiple melanomas and pancreatic carcinoma but also of breast cancer.
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| 3. |
- Borg, Åke, et al.
(author)
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Novel germline p16 mutation in familial malignant melanoma in southern Sweden
- 1996
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In: Cancer Research. - 0008-5472. ; 56:11, s. 500-2497
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Journal article (peer-reviewed)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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| 4. |
- Måsbäck, A, et al.
(author)
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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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In: Melanoma Research. - 0960-8931. ; 9:2, s. 97-189
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Journal article (peer-reviewed)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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| 5. |
- Pandis, N, et al.
(author)
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Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases
- 1996
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In: International Journal of Cancer. - 0020-7136. ; 66:2, s. 6-191
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Journal article (peer-reviewed)abstract
- A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grade and mitotic activity of the tumor. Whereas all lobular carcinomas were karyotypically normal or near-diploid, more than 3 aberrations and sometimes near-triploid or near-tetraploid karyotypes were common findings in ductal carcinomas, especially in grade-III tumors and in tumors showing high mitotic activity in vivo. Karyotypes with cytogenetically unregulated clones and unbalanced structural chromosomal rearrangements were more frequent in infiltrating than in in situ carcinomas but, at least as far as the second of these 2 characteristics is concerned, especially in infiltrating carcinomas that also had an in situ component. The presence of cytogenetic polyclonality correlated with tumor grade. Although recurrent chromosome aberrations were significantly more common in ductal than in lobular carcinomas, none of these breast cancer-associated anomalies seemed to be specific for any particular clinicopathologic parameter. The associations between modal chromosome number and mitotic activity and between cytogenetic polyclonality and tumor grade were found to be statistically significant in multivariate models. No correlations was seen between the karyotypic findings and tumor size or the presence of axillary-lymph-node metastases.
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| 6. |
- Petersson, C, et al.
(author)
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Chromosome aberrations in prophylactic mastectomies from women belonging to breast cancer families
- 1996
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In: Genes, Chromosomes and Cancer. - 1045-2257. ; 16:3, s. 185-188
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Journal article (peer-reviewed)abstract
- Short-term cultures of samples from eight prophylactic mastectomies from five unrelated women who were genetically predisposed to breast cancer were analyzed cytogenetically. Clonal chromosome abnormalities were detected in five breasts. Three samples from two women had aberrations involving the short arm of chromosome 3, with a breakpoint in 3p14 in common. Three samples from three women had rearrangements of 1q. Two of them, one of which also displayed a 3p14 rearrangement, shared a breakpoint in 1q41. Both 1q41 and, in particular, 3p14 have been reported to be rearranged frequently in malignant breast proliferations. Whether alterations of genes in these bands are essential in mammary tumorigenesis and, if so, whether they are equally important in sporadic and in hereditary cases remains to be explored.
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| 7. |
- Westerdahl, J, et al.
(author)
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Is the use of sunscreens a risk factor for malignant melanoma?
- 1995
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In: Melanoma Research. - 0960-8931. ; 5:1, s. 59-65
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Journal article (peer-reviewed)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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| 8. |
- Westerdahl, J, et al.
(author)
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Reproducibility of a self-administered questionnaire for assessment of melanoma risk
- 1996
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In: International Journal of Epidemiology. - 0300-5771. ; 25:2, s. 245-251
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Journal article (peer-reviewed)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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| 9. |
- Westerdahl, J, et al.
(author)
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Risk of cutaneous malignant melanoma in relation to use of sunbeds : further evidence for UV-A carcinogenicity
- 2000
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:9, s. 1593-1599
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Journal article (peer-reviewed)abstract
- In a population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma and 913 healthy controls aged 16-80 years, the association between sunbed use and malignant melanoma was evaluated. A total of 250 (44%) cases and 372 (41%) controls reported ever having used sunbeds. A significantly elevated odds ratio for developing malignant melanoma after regular exposure to sunbeds was found, adjusted for hair colour, raised naevi, skin type and number of sunburns (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-2.7). A dose-response relationship between total number of sunbed uses and melanoma risk was only found up to the level of 250 times. The OR was higher in individuals younger than age 36 years (adjusted OR 8.1, 95% CI 1.3-49.5 for regular vs. never use). The association seemed to be true only for subjects with black/dark brown or light brown hair and among females. Lesions of the extremities showed the strongest association of increased risk with sunbed use. An increased risk was related to commercial exposure and to exposure during the winter. The results substantiate the hypothesis that exposure to sunbeds might increase the risk of developing malignant melanoma.
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| 10. |
- Westerdahl, J, et al.
(author)
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Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors
- 1996
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In: British Journal of Cancer. - 0007-0920. ; 73:9, s. 31-1126
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Journal article (peer-reviewed)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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