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- Bahmanyar, S., et al.
(författare)
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Cancer risk among patients with multiple sclerosis and their parents
- 2009
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Ingår i: Neurology. - Minneapolis, Minn. : Lancet Publications Inc.. - 0028-3878 .- 1526-632X. ; 72:13, s. 1170-1177
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).
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| 5. |
- Fogdell, A, et al.
(författare)
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Linkage analysis of HLA class II genes in Swedish multiplex families with multiple sclerosis
- 1997
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 48:3, s. 758-762
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Tidskriftsartikel (refereegranskat)abstract
- Article abstract-We assessed the influence of human leukocyte antigen (HLA) class II as susceptibility genes in multiple sclerosis (MS) by linkage analysis. Other research groups, who have shown negative results in studies on affected sibling pairs, have questioned the influence of the HLA class II genes, although they confirmed the association of the DR15,DQ6,Dw2 haplotype to MS. In this report, we find a significant lod score (>3) when using a 2-point linkage analysis of 49 small Swedish nuclear MS families with at least two affected family members, typed for HLA class II alleles by PCR amplification with sequence-specific primers. We obtained maximum lod scores when we used dominant or intermediate models with low penetrance. We found that the positive effect on the total lod score was not confined to those families carrying the presumed susceptibility HLA-haplotype Dw2. This observation supports the notion of a functional role of the HLA class II molecules themselves in MS. In addition, we observed significant transmission distortion and an intrafamilial association of the MS-associated class II haplotype HLA-Dw2. These results indicate that the HLA class II genes are of clear importance for MS in the studied population.NEUROLOGY 1997;48: 758-762
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| 6. |
- Hensiek, A E, et al.
(författare)
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Familial effects on the clinical course of multiple sclerosis.
- 2007
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 68:5, s. 376-83
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
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