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- Borg, Åke, et al.
(författare)
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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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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 92:15, s. 6-1260
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Malander, S, et al.
(författare)
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One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations : results of a prospective study in Southern Sweden
- 2004
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 40:3, s. 422-428
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Tidskriftsartikel (refereegranskat)abstract
- At least 10% of all ovarian cancers are estimated to have a hereditary background. Hereditary breast-ovarian cancer (HBOC) due to mutations in the BRCA genes is a major cause of hereditary ovarian cancer, although its frequency and relationship to age and family history in unselected series of ovarian cancers is not completely known. We report here the results of a full mutational screening analysis for germ line BRCA1 and BRCA2 mutations in 161 patients with invasive epithelial ovarian carcinomas. Age at diagnosis ranged from 22 to 82 years (mean 59 years). Deleterious (frame-shift, nonsense and missense) mutations were detected in 13/161 (8%) of the patients and affected BRCA1 in 12 cases and BRCA2 in one case. Four additional missense variants (one in BRCA1 and three in BRCA2) with a possible association with an increased risk ovarian cancer were revealed, resulting in a total frequency of BRCA gene alterations of 17/161 (11%). The 13 patients with deleterious mutations had a mean age of 57 years (range 41-76 years) and only three of these patients were below 50 years of age. A family history of at least one breast cancer and/or ovarian cancer was reported in all but 1 of the patients with BRCA mutations compared with only 24% of patients without mutations. Our findings in this prospective study confirm approximately 1 in 10 patients with ovarian cancer carry a germ line BRCA gene mutation associated with HBOC, and also indicate that a large number of these patients are over 50 years of age at diagnosis.
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| 3. |
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| 4. |
- Westerdahl, J, et al.
(författare)
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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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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:9, s. 1593-1599
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Tidskriftsartikel (refereegranskat)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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