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Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Rheumatology)
2008 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, Vol. 58, no 1, 302-7 p.Article in journal (Other academic) Published
Abstract [en]

OBJECTIVE: The etiology of Wegener's granulomatosis (WG) supposedly involves interplay between genetic susceptibility and environmental triggers. However, little is known about whether WG actually clusters in families. Information on the degree of familial aggregation in WG is of clinical relevance, because patients with WG often want to know whether their diagnosis puts their closest relatives at increased risk of the disease. The aim of this study was to investigate the risk of WG in relatives of patients with WG. METHODS: Using Swedish nationwide registers on morbidity, family structure, and vital status, we compared the occurrence of WG (register-based plus chart review) among 6,670 first-degree relatives and 428 spouses of 1,944 Swedish patients with WG with the occurrence among 68,994 first-degree relatives and 4,812 spouses of 19,655 control subjects from the general population. Relative risks were estimated using the Cox proportional hazards regression model. RESULTS: Two of the 6,670 first-degree relatives of patients with WG and 13 of the 68,994 first-degree relatives of their population controls had WG, resulting in a relative risk of 1.56 (95% confidence interval 0.35-6.90). None of the 428 spouses of patients had WG. CONCLUSION: In absolute terms, the occurrence of WG among close biologic and nonbiologic relatives of patients with WG is low. In terms of relative risk, our results provide strong evidence against a pronounced increase in familial risk such as that noted for systemic lupus erythematosus, irritable bowel disease, and multiple sclerosis but are compatible with familial aggregation of a magnitude similar to that for rheumatoid arthritis.

Place, publisher, year, edition, pages
2008. Vol. 58, no 1, 302-7 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-14211DOI: 10.1002/art.23157ISI: 000252733100034PubMedID: 18163522OAI: oai:DiVA.org:uu-14211DiVA: diva2:41981
Available from: 2008-01-29 Created: 2008-01-29 Last updated: 2013-09-19Bibliographically approved
In thesis
1. Clinical and Epidemiological Studies of Wegener´s Granulomatosis
Open this publication in new window or tab >>Clinical and Epidemiological Studies of Wegener´s Granulomatosis
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Wegener´s granulomatosis (WG) is an unusual, serious, systemic vasculitis with specific clinical findings. The studies in this thesis aim at broadening our understanding of the aetiology and outcome of WG.

Patients with WG were identified in the In-patient Register 1975-2001. During this time the incidence increased three-fold, and neither ANCA-related increased awareness, nor diagnostic drift, seem to fully explain this trend, but it is still unclear if a true rise in incidence exists.

Anti- neutrophil cytoplasmic antibodies (ANCA) have been presented as highly specific for vasculitis. In a series of consecutive cANCA/PR3-ANCA positive patients, we investigated the positive predictive value for ANCA, and the outcome of patients with a positive cANCA/PR3-ANCA but not vasculitis. These patients have a low future risk of developing vasculitis, possibly indicating that ANCA, in this setting, reflects neutrophil activating properties not specific to vasculitis.

By linkage of the WG-cohort, and randomly selected population controls, to the Multi-generation register, we identified all first-degree relatives and spouses of patients and controls, totally encompassing some 2,000 patients and 70,000 relatives. Familial aggregation of WG was the exception, with absolute risks of < 1 per 1000.However, relative risks in first-grade relatives amounted to 1.56 (95% CI 0.35-6.90) such that a moderate familial aggregation cannot be excluded.

In the WG-cohort, cancer occurrence and risk was compared to that of the general population. Patients with WG have an overall doubled risk of cancer, with particularly increased risks of bladder-cancer, haematopoietic cancers including lymphomas and squamous skin-cancer. In a case-control study nested within the WG-cohort, treatment with cyclophosphamide was compared among bladder-cancer patients and matched cancer-free controls. Absolute risk of bladder cancer as high as 10% some years after diagnosis were found, and this risk can partly be attributed to cyclophosphamide-treatment, with a dose-response relationship.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 80 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 258
Medicine, Wegener´s granulomatosis, incidence, time-trends, ANCA, familial aggregation, cancer risks, bladder cancer, cyclophosphamide, Medicin
urn:nbn:se:uu:diva-7887 (URN)978-91-554-6892-7 (ISBN)
Public defence
2007-05-31, Robergsalen, Ingång 40, Akademiska Sjukhuset, Uppsala, 09:15
Available from: 2007-05-10 Created: 2007-05-10 Last updated: 2013-09-19Bibliographically approved

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